Triazole derivatives useful as Axl inhibitors

ABSTRACT

Methods of using triazole derivatives in treating diseases or conditions associated with Axl catalytic activity are disclosed.

CROSS-REFERENCE(S) TO RELATED APPLICATION(S)

This application is a divisional of U.S. patent application Ser. No.11/518,550, filed Sep. 7, 2006 (now allowed); which claims the benefitunder 35 U.S.C. §119(e) of U.S. Provisional Patent Application No.60/714,673, filed Sep. 7, 2005; U.S. Provisional Patent Application No.60/780,166, filed Mar. 7, 2006; and U.S. Provisional Patent ApplicationNo. 60/813,143, filed Jun. 12, 2006. These applications are incorporatedherein by reference in their entireties.

FIELD OF THE INVENTION

This invention is directed to triazole derivatives and pharmaceuticalcompositions thereof which are useful as inhibitors of the receptorprotein tyrosine kinase known as Axl. This invention is also directed tomethods of using the derivatives and compositions in treating diseasesand conditions associated with Axl activity, particularly in treatingdiseases and conditions associated with angiogenesis and/or cellproliferation.

BACKGROUND OF THE INVENTION

All of the protein kinases that have been identified to date in thehuman genome share a highly conserved catalytic domain of around 300 aa.This domain folds into a bi-lobed structure in which reside ATP-bindingand catalytic sites. The complexity of protein kinase regulation allowsmany potential mechanisms of inhibition including competition withactivating ligands, modulation of positive and negative regulators,interference with protein dimerization, and allosteric or competitiveinhibition at the substrate or ATP binding sites.

Axl (also known as UFO, ARK, and Tyro7; nucleotide accession numbersNM_(—)021913 and NM_(—)001699; protein accession numbers NP_(—)068713and NP_(—)001690) is a receptor protein tyrosine kinase (RTK) thatcomprises a C-terminal extracellular ligand-binding domain andN-terminal cytoplasmic region containing the catalytic domain. Theextracellular domain of Axl has a unique structure that juxtaposesimmunoglobulin and fibronectin Type III repeats and is reminiscent ofthe structure of neural cell adhesion molecules. Axl and its two closerelatives, Mer/Nyk and Sky (Tyro3/Rse/Dtk), collectively known as theTyro3 family of RTKs, all bind and are stimulated to varying degrees bythe same ligand, Gas6 (growth arrest specific-6), a ˜76 kDa secretedprotein with significant homology to the coagulation cascade regulator,Protein S. In addition to binding to ligands, the Axl extracellulardomain has been shown to undergo homophilic interactions that mediatecell aggregation, suggesting that one important function of Axl may beto mediate cell-cell adhesion.

Axl is predominantly expressed in the vasculature in both endothelialcells (ECs) and vascular smooth muscle cells (VSMCs) and in cells of themyeloid lineage and is also detected in breast epithelial cells,chondrocytes, Sertoli cells and neurons. Several functions includingprotection from apoptosis induced by serum starvation, TNF-α or theviral protein E1A, as well as migration and cell differentiation havebeen ascribed to Axl signaling in cell culture. However, Axl−/− miceexhibit no overt developmental phenotype and the physiological functionof Axl in vivo is not clearly established in the literature.

Angiogenesis (the formation of new blood vessels) is limited tofunctions such as wound healing and the female reproductive cycle inhealthy adults. This physiological process has been co-opted by tumors,thus securing an adequate blood supply that feeds tumor growth andfacilitates metastasis. Deregulated angiogenesis is also a feature ofmany other diseases (for example, psoriasis, rheumatoid arthritis,endometriosis and blindness due to age-related macular degeneration(AMD), retinopathy of prematurity and diabetes) and often contributes tothe progression or pathology of the condition.

The overexpression of Axl and/or its ligand has also been reported in awide variety of solid tumor types including, but not limited to, breast,renal, endometrial, ovarian, thyroid, non-small cell lung carcinoma, anduveal melanoma as well as in myeloid leukemias. Furthermore, itpossesses transforming activity in NIH3T3 and 32D cells. It has beendemonstrated that loss of Axl expression in tumor cells blocks thegrowth of solid human neoplasms in an in vivo MDA-MB-231 breastcarcinoma xenograft model. Taken together, these data suggest Axlsignaling can independently regulate EC angiogenesis and tumor growthand thus represents a novel target class for tumor therapeuticdevelopment.

The expression of Axl and Gas6 proteins is upregulated in a variety ofother disease states including endometriosis, vascular injury and kidneydisease and Axl signaling is functionally implicated in the latter twoindications. Axl-Gas6 signaling amplifies platelet responses and isimplicated in thrombus formation. Axl may thus potentially represent atherapeutic target for a number of diverse pathological conditionsincluding solid tumors, including, but not limited to, breast, renal,endometrial, ovarian, thyroid, non-small cell lung carcinoma and uvealmelanoma; liquid tumors, including but not limited to, leukemias(particularly myeloid leukemias) and lymphomas; endometriosis, vasculardisease/injury (including but not limited to restenosis, atherosclerosisand thrombosis), psoriasis; visual impairment due to maculardegeneration; diabetic retinopathy and retinopathy of prematurity;kidney disease (including but not limited to glomerulonephritis,diabetic nephropathy and renal transplant rejection), rheumatoidarthritis; osteoarthritis and cataracts.

SUMMARY OF THE INVENTION

This invention is directed to certain triazole derivatives which areuseful as Axl inhibitors, methods of using such derivatives in treatingdiseases and conditions associated with Axl activity and pharmaceuticalcompositions comprising such derivatives.

Accordingly, in one aspect this invention is directed to compounds offormula (Ia) or formula (Ib):

-   wherein, independently at each occurrence:-   A is —C(O)—;-   or A is selected from the group consisting of —C(S)—, —C(NR¹¹)—,    —C(O)O—, —C(S)O—, —C(O)S—, —C(S)S—, —C(S)S—, —C(NR¹¹)S—, —C(NR¹¹)O—,    —C(S)N(R⁶), —C(O)N(R⁶)— and —C(NR¹¹)N(R⁶)—;-   R¹ is one of the following:    -   a) aryl optionally substituted with one or more substituents        selected from the group consisting of halo, haloalkyl, alkyl,        optionally substituted heteroaryl, optionally substituted        heterocyclyl, —R⁸—OR¹⁰, —R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰,        —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶        (where p is 0, 1 or 2), —R⁸—O—R⁹—N(R⁶)R⁷,        —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and —R⁸—N(R⁶)C(O)R¹⁰; or    -   b) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, halo,        oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁶)R⁷; or    -   c) heterocyclyl optionally substituted with one or more        substituents selected from the group consisting of halo,        haloalkyl, alkyl, oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷,        —R⁸—S(O)_(p)R¹⁰ (where p is 0, 1 or 2) and —R⁸—N(R⁶)R⁷;    -   d) heterocyclylalkyl optionally substituted with one or more        substitutents selected from the group consisting of halo,        haloalkyl, alkyl, optionally substituted aryl, optionally        substituted aralkyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and        —R⁸—N(R⁶)R⁷; or    -   e) cycloalkyl optionally substituted with one or more        substituents selected from the group consisting of halo,        haloalkyl, alkyl, oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷,        —R⁸—S(O)_(p)R¹⁰ (where p is 0, 1 or 2) and —R⁸—N(R⁶)R⁷;-   R², R⁴ and R⁵ are each independently hydrogen, alkyl, aryl, aralkyl,    —C(O)R¹⁰ or —C(O)N(R⁶)R⁷;-   R³ is one of the following:    -   a) alkyl optionally substituted with one or more substituents        selected from the group consisting of halo, cyano, nitro, oxo,        thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,        —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,        —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t        is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and        —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is        independently hydrogen, alkyl, haloalkyl, cycloalkyl,        cycloalkylalkyl, aryl (optionally substituted with one or more        halo groups), aralkyl, heterocyclyl, heterocylylalkyl,        heteroaryl or heteroarylalkyl;    -   b) cycloalkyl optionally substituted with one or more        substituents selected from the group consisting of —R⁸—OR¹⁰,        alkyl, halo, haloalkyl, aryl, and aralkyl;    -   c) aryl optionally substituted with one or more substituents        selected from the group consisting of alkyl, halo, haloalkyl,        nitro, cycloalkyl, cycloalkylalkyl, optionally substituted aryl,        optionally substituted heteroaryl, optionally substituted        heterocyclyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,        —R⁸—O—R⁶—C(O)OR¹⁰, —R⁸—O—R⁶—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is        0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,        —R⁸—N(R⁶)C(O)R¹⁰, —R⁸—N(R⁸)C(O)OR¹⁰ and —R⁸—CN;    -   d) aralkyl, wherein:        -   (1) the alkyl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of halo, cyano, nitro, oxo, thioxo,            trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,            —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,            —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where            t is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and            —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is            independently hydrogen, alkyl, haloalkyl, cycloalkyl,            cycloalkylalkyl, aryl (optionally substituted with one or            more halo groups), aralkyl, heterocyclyl, heterocylylalkyl,            heteroaryl or heteroarylalkyl; and        -   (2) the aryl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of alkyl, alkenyl, alkynyl, halo,            haloalkyl, haloalkenyl, haloalkynyl, cyano, nitro, aryl,            aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl,            cycloalkylalkenyl, cycloalkylalkynyl, heterocyclyl,            heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl,            heteroaryl, heteroarylalkyl, heteroarylalkenyl,            heteroarylalkynyl, —R¹⁵—OR¹⁴, —R¹⁵—OC(O)—R¹⁴, —R¹⁵—N(R¹⁴)₂,            —R¹⁵—C(O)R¹⁴, —R¹⁵—C(O)OR¹⁴, —R¹⁵—C(O)N(R¹⁴)₂,            —R¹⁵—O—R¹⁶—C(O)N(R¹⁴)₂, —R¹⁵—N(R¹⁴)C(O)OR¹⁴,            —R¹⁵—N(R¹⁴)C(O)R¹⁴, —R¹⁵—N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or            2), —R¹⁵—S(O)_(t)OR¹⁴ (where t is 1 or 2), —R¹⁵—S(O)_(p)R¹⁴            (where p is 0, 1 or 2), and —R¹⁵—S(O)_(t)N(R¹⁴)₂ (where t is            1 or 2), where each R¹⁴ is independently hydrogen, alkyl,            haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl,            heterocyclyl, heterocyclylalkyl, heteroaryl or            heteroarylalkyl, each R¹⁵ is independently a direct bond or            a straight or branched alkylene or alkenylene chain, and R¹⁶            is a straight or branched alkylene or alkenylene chain;    -   e) optionally substituted aralkenyl;    -   f) optionally substituted aralkynyl;    -   g) optionally substituted heteroaryl;    -   h) optionally substituted heteroarylalkenyl; or    -   i) optionally substituted heteroarylalkynyl;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰;-   as an isolated stereoisomer or tautomer thereof or mixtures thereof,-   or a pharmaceutically acceptable salt, hydrate, solvate, N-oxide or    prodrug thereof;-   provided that for compounds of formula (Ia):    -   a) when A is —C(O)—, R², R⁴ and R⁵ are all hydrogen, and R³ is        3,4,5-trimethoxyphenyl, R¹ is not pyridin-3-yl;    -   b) when A is —C(O)—, R², R⁴ and R⁵ are all hydrogen, and R¹ is        unsubstituted phenyl, R³ is not unsubstituted phenyl,        unsubstituted 1,3-benzodioxol-5-yl, 2-(furan-2-yl)ethenyl,        4-chlorophenyl, unsubstituted naphthyl, 3-bromophenyl,        4-phenylphenyl, 4-trifluoromethylphenyl, 3-nitrophenyl,        3-(phenylcarbonyl)phenyl, 4-phenylbenzyl, 3-phenoxyphenyl,        unsubstituted cyclohexyl, unsubstituted benzyl, unsubstituted        pyridin-3-yl, 3,5-dichlorophenyl, 4-acetylphenyl, 4-nitrophenyl,        4-fluorobenzyl, 2,6-difluorophenyl, 2-phenoxyphenyl,        3-methoxyphenyl, 2-methoxyphenyl, 4-methylphenyl or        unsubstituted furan-2-yl;    -   c) when A is —C(O)—, R², R⁴ and R⁵ are all hydrogen, and R³ is        unsubstituted phenyl, R¹ is not 2-methyl-5-chlorophenyl,        3-chlorophenyl, or 3,4,5-trimethoxyphenyl;    -   d) when A is —C(O)—, R², R⁴ and R⁵ are all hydrogen, and R³ is        2,6-difluorophenyl, is not 3-chlorophenyl,        4-(4-methylpiperidin-1-yl)phenyl, 4-(imidazol-1-yl)phenyl,        4-(1,2,4-triazol-1-yl)phenyl, 4-(1,2,4-triazol-4-yl)phenyl,        4-(imidazolidin-2-on-1-yl)phenyl, or        4-(1,1-dioxidoisothiazolidin-2-yl)phenyl;    -   e) when A is —C(O)—, R², R⁴ and R⁵ are all hydrogen, and R¹ is        4-(4-methylpiperidin-1-yl)phenyl, R³ is not        2,6-difluoro-3-methylphenyl, 3-methylthien-2-yl,        2,4-dimethylthien-2-yl, or 2-ethylthien-2-yl;    -   f) when A is —C(O)—, R², R⁴ and R⁵ are all hydrogen, and R¹ is        4-(imidazol-1-yl)phenyl, R³ is not 5-ethylthien-2-yl,        3-methylthien-2-yl, 2,5-dimethylthien-2-yl, or        2,6-difluoro-3-methylphenyl;    -   g) when A is —C(O)—, R², R⁴ and R⁵ are all hydrogen, and R¹ is        3-chlorophenyl, R³ is not 2-(phenylcarbonyl)ethyl,        3-phenylpropyl, 2-phenylethyl, naphth-2-ylmethyl or        2-(phenylcarbonyl)propyl;    -   h) when A is —C(O)—, R², R⁴ and R⁵ are all hydrogen, and R¹ is        4-(1,2,4-triazol-1-yl)phenyl, R³ is not        2,6-difluoro-3-methylphenyl, 3-methylthien-2-yl,        3,5-dimethylthien-2-yl, or 5-ethylthien-2-yl;    -   i) when A is —C(O)—, R², R⁴ and R⁵ are all hydrogen, and R¹ is        4-(1,2,4-triazol-4-yl)phenyl, R³ is not 3-methylthien-2-yl or        2,6-difluoro-3-methylphenyl;    -   j) when A is —C(O)—, R², R⁴ and R⁵ are all hydrogen, and R¹ is        4-(imidazolidin-2-on-1-yl)phenyl, R³ is not 3-methylthien-2-yl        or 2,6-difluoro-3-methylphenyl;    -   k) when A is —C(O)—, R², R⁴ and R⁵ are all hydrogen, and R¹ is        4-(1,1-dioxidoisothiazolidin-2-yl)phenyl, R³ is not        3-methylthien-2-yl;    -   l) when A is —C(O)—, R², R⁴ and R⁵ are all hydrogen, and R³ is        2-chlorophenyl, R¹ is not 6-methoxypyridin-3-yl or        4-methoxyphenyl;    -   m) when A is —C(O)—, R², R⁴ and R⁵ are all hydrogen, and R³ is        unsubstituted pyridin-3-yl, R¹ is not 6-methoxypyridin-3-yl;    -   m) when A is —C(O)—, R², R⁴ and R⁵ are all hydrogen, and R³ is        4-nitrophenyl, R¹ is not 4-methyl-2,4-dihydrothiazol-2-yl;    -   o) when A is —C(O)—, R², R⁴ and R⁵ are all hydrogen, and R¹ is        4-methoxyphenyl, R³ is not thien-2-yl or furan-2-yl;    -   p) when A is —C(O)N(H)—, R², R⁴ and R⁵ are all hydrogen, and R¹        is unsubstituted phenyl, R³ is not unsubstituted phenyl,        unsubstituted cyclohexyl, 4-phenylphenyl, 4-phenoxyphenyl,        2-methyl-4-bromophenyl, unsubstituted naphth-1-yl,        3-nitrophenyl, or 3-methoxyphenyl;    -   q) when A is —C(O)N(H)—, R², R⁴ and R⁵ are all hydrogen, and R¹        is 4-chlorophenyl, R³ is not 4-methoxyphenyl;    -   r) when A is —C(O)N(H)—, R², R⁴ and R⁵ are all hydrogen, and R³        is unsubstituted phenyl, R¹ is not unsubstituted pyridin-3-yl or        3,4,5-trimethoxyphenyl; or    -   s) when A is —C(O)N(H)—, R², R⁴ and R⁵ are all hydrogen, and R¹        is unsubstituted pyridin-3-yl, R³ is not unsubstituted benzyl,        2-chlorophenyl, 3-chlorophenyl, or 4-methylphenyl;-   and provided that for compounds of formula (Ib):    -   t) when A is —C(O)—, R², R⁴ and R⁵ are all hydrogen, and R¹ is        unsubstituted phenyl, R³ is not 2-(furan-2-yl)ethenyl,        unsubstituted phenyl, or 2,6-difluorophenyl;    -   u) when A is —C(O)—, R², R⁴ and R⁵ are all hydrogen, and R¹ is        3-chlorophenyl, R³ is not unsubstituted phenyl or        2,6-difluorophenyl;    -   v) when A is —C(O)N(H)—, R², R⁴ and R⁵ are all hydrogen, R¹ is        unsubstituted phenyl, R³ is not 3,4,5-trimethoxyphenyl; or    -   w) when A is —C(O)N(H)—, R², R⁴ and R⁵ are all hydrogen, R¹ is        4-methylphenyl, R³ is not pyridin-3-yl.

In another aspect, this invention provides assays to determine acompound of the invention effectiveness in inhibiting Axl activity in acell-based assay.

In another aspect, the following compounds, as identified by theirunique Chemical Abstracts Service (CAS) registry numbers, are not meantto be included within the scope of the invention: 110984-61-7;324074-12-6; 324074-13-7; 324074-14-8; 324074-15-9; 324074-16-0;324074-17-1; 324074-18-2; 324074-19-3; 324074-20-6; 324074-21-7;324074-22-8; 324074-23-9; 324074-24-0; 324074-25-1; 324074-28-4;324074-29-5; 324074-30-8; 324074-31-9; 324074-32-0; 324074-33-1;324074-34-2; 324074-35-3; 324074-36-4; 324074-38-6; 324074-39-7;324074-41-1; 324074-42-2; 324074-43-3; 324074-44-4; 324074-45-5;324074-46-6; 324074-47-7; 324074-48-8; 324074-50-2; 324074-51-3;324074-52-4; 443798-64-9; 443798-65-0; 443798-66-1; 443798-67-2;443798-68-3; 443798-69-4; 443798-70-7; 443798-71-8; 443798-72-9;443798-73-0; 443798-74-1; 443798-87-6; 443798-88-7; 443798-89-8;443798-90-1; 443798-91-2; 443798-92-3; 443798-93-4; 443798-96-7;443798-95-6; 443798-94-5; 443798-97-8; 443798-98-9; 443798-99-0;443799-10-8; 443799-12-0; 443799-14-2; 443799-16-4; 443799-18-6;503546-63-2; 503546-65-4; 700811-45-6; 700812-30-2; 700812-68-6;700812-69-7; 863030-86-8; 863030-85-7; 863030-84-6; 863030-77-7;863030-76-6; 863030-74-4; 863030-87-9; 863030-83-5; 863030-81-3; and863030-79-9.

In another aspect, the scope of the invention is not meant to includeany compounds disclosed or claimed in the following publications,patents and patent applications:

-   U.S. Pat. No. 3,813,400;-   PCT Published Patent Application No. WO 01/09106;-   PCT Published Patent Application No. WO 02/057240;-   PCT Published Patent Application No. WO 03/027275;-   PCT Published Patent Application No. WO 03/093344-   PCT Published Patent Application No. WO 2004/017997;-   PCT Published Patent Application No. WO 2004/046120;-   PCT Published Patent Application No. WO 2005/077922;-   Katrizky, A. R. et al., “Synthesis of    5-(2-arylazenyl)-1,2,4-triazoles and    2-amino-5-aryl-1,3,4-oxadiazoles”, ARKIVOC (2002), vi, pp. 82-90;    and-   Reiter, J. et al., “On triazoles. VI. The acylation of    5-amino-1,2,4-triazoles”, Journal of Heterocyclic Chemistry (1987),    24(1), pp. 127-42.

DETAILED DESCRIPTION OF THE INVENTION Definitions

As used in the specification and appended claims, unless specified tothe contrary, the following terms have the meaning indicated:

“Amino” refers to the —NH₂ radical.

“Cyano” refers to the —CN radical.

“Nitro” refers to the —NO₂ radical.

“Oxa” refers to the —O— radical.

“Oxo” refers to the ═O radical.

“Thioxo” refers to the ═S radical.

“Alkyl” refers to a straight or branched hydrocarbon chain radicalconsisting solely of carbon and hydrogen atoms, containing nounsaturation, having from one to twelve carbon atoms, preferably one toeight carbon atoms or one to six carbon atoms, and which is attached tothe rest of the molecule by a single bond, for example, methyl, ethyl,n-propyl, 1-methylethyl (iso-propyl), n-butyl, n-pentyl,1,1-dimethylethyl (t-butyl), 3-methylhexyl, 2-methylhexyl, and the like.Unless stated otherwise specifically in the specification, an alkylgroup may be optionally substituted by one or more of the followingsubstituents: halo, cyano, nitro, oxo, thioxo, trimethylsilanyl, —OR¹⁴,—OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴, —C(O)OR¹⁴, —C(O)N(R¹⁴)₂,—N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴, —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2),—S(O)_(t)OR¹⁴ (where t is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2),and —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is independentlyhydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl(optionally substituted with one or more halo groups), aralkyl,heterocyclyl, heterocylylalkyl, heteroaryl or heteroarylalkyl, and whereeach of the above substituents is unsubstituted unless otherwiseindicated.

“Alkenyl” refers to a straight or branched hydrocarbon chain radicalgroup consisting solely of carbon and hydrogen atoms, containing atleast one double bond, having from two to twelve carbon atoms,preferably one to eight carbon atoms and which is attached to the restof the molecule by a single bond, for example, ethenyl, prop-1-enyl,but-1-enyl, pent-1-enyl, penta-1,4-dienyl, and the like. Unless statedotherwise specifically in the specification, an alkenyl group may beoptionally substituted by one or more of the following substituents:halo, cyano, nitro, oxo, thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴,—N(R¹⁴)₂, —C(O)R¹⁴, C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴,—N(R¹⁴)C(O)R¹⁴, N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴(where t is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and—S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is independentlyhydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl(optionally substituted with one or more halo groups), aralkyl,heterocyclyl, heterocylylalkyl, heteroaryl or heteroarylalkyl, and whereeach of the above substituents is unsubstituted unless otherwiseindicated.

“Alkynyl” refers to a straight or branched hydrocarbon chain radicalgroup consisting solely of carbon and hydrogen atoms, containing atleast one triple bond, optionally containing at least one double bond,having from two to twelve carbon atoms, preferably one to eight carbonatoms and which is attached to the rest of the molecule by a singlebond, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, andthe like. Unless stated otherwise specifically in the specification, analkynyl group may be optionally substituted by one or more of thefollowing substituents: halo, cyano, nitro, oxo, thioxo,trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴, —C(O)OR¹⁴,—C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴, —N(R¹⁴)S(O)_(t)R¹⁴ (wheret is 1 or 2), —S(O)_(t)OR¹⁴ (where t is 1 or 2), —S(O)_(p)R¹⁴ (where pis 0, 1 or 2), and —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴is independently hydrogen, alkyl, haloalkyl, cycloalkyl,cycloalkylalkyl, aryl (optionally substituted with one or more halogroups), aralkyl, heterocyclyl, heterocylylalkyl, heteroaryl orheteroarylalkyl, and where each of the above substituents isunsubstituted unless otherwise indicated.

“Alkylene” or “alkylene chain” refers to a straight or branched divalenthydrocarbon chain linking the rest of the molecule to a radical group,consisting solely of carbon and hydrogen, containing no unsaturation andhaving from one to twelve carbon atoms, for example, methylene,ethylene, propylene, n-butylene, and the like. The alkylene chain isattached to the rest of the molecule through a single bond and to theradical group through a single bond. The points of attachment of thealkylene chain to the rest of the molecule and to the radical group canbe through one carbon in the alkylene chain or through any two carbonswithin the chain. Unless stated otherwise specifically in thespecification, an alkylene chain may be optionally substituted by one ormore of the following substituents: halo, cyano, nitro, aryl,cycloalkyl, heterocyclyl, heteroaryl, oxo, thioxo, trimethylsilanyl,—OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, C(O)R¹⁴, —C(O)OR¹⁴, —C(O)N(R¹⁴)₂,—N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴, —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2),—S(O)_(t)OR¹⁴ (where t is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2),and —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is independentlyhydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl(optionally substituted with one or more halo groups), aralkyl,heterocyclyl, heterocylylalkyl, heteroaryl or heteroarylalkyl, and whereeach of the above substituents is unsubstituted unless otherwiseindicated.

“Alkenylene” or “alkenylene chain” refers to a straight or brancheddivalent hydrocarbon chain linking the rest of the molecule to a radicalgroup, consisting solely of carbon and hydrogen, containing at least onedouble bond and having from two to twelve carbon atoms, for example,ethenylene, propenylene, n-butenylene, and the like. The alkenylenechain is attached to the rest of the molecule through a double bond or asingle bond and to the radical group through a double bond or a singlebond. The points of attachment of the alkenylene chain to the rest ofthe molecule and to the radical group can be through one carbon or anytwo carbons within the chain. Unless stated otherwise specifically inthe specification, an alkenylene chain may be optionally substituted byone or more of the following substituents: halo, cyano, nitro, aryl,cycloalkyl, heterocyclyl, heteroaryl, oxo, thioxo, trimethylsilanyl,—OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴, —C(O)OR¹⁴, —C(O)N(R¹⁴)₂,—N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴, N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2),—S(O)_(t)OR¹⁴ (where t is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2),and —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is independentlyhydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl(optionally substituted with one or more halo groups), aralkyl,heterocyclyl, heterocylylalkyl, heteroaryl or heteroarylalkyl, and whereeach of the above substituents is unsubstituted unless otherwiseindicated.

“Alkynylene” or “alkynylene chain” refers to a straight or brancheddivalent hydrocarbon chain linking the rest of the molecule to a radicalgroup, consisting solely of carbon and hydrogen, containing at least onetriple bond and having from two to twelve carbon atoms, for example,propynylene, n-butynylene, and the like. The alkynylene chain isattached to the rest of the molecule through a single bond and to theradical group through a double bond or a single bond. The points ofattachment of the alkynylene chain to the rest of the molecule and tothe radical group can be through one carbon or any two carbons withinthe chain. Unless stated otherwise specifically in the specification, analkynylene chain may be optionally substituted by one or more of thefollowing substituents: alkyl, alkenyl, halo, haloalkenyl, cyano, nitro,aryl, cycloalkyl, heterocyclyl, heteroaryl, oxo, thioxo,trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴, —C(O)OR¹⁴,—C(O)N(R¹⁴)₂, N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴, —N(R¹⁴)S(O)_(t)R¹⁴ (wheret is 1 or 2), —S(O)_(t)OR¹⁴ (where t is 1 or 2), —S(O)_(p)R¹⁴ (where pis 0, 1 or 2), and —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴is independently hydrogen, alkyl, haloalkyl, cycloalkyl,cycloalkylalkyl, aryl (optionally substituted with one or more halogroups), aralkyl, heterocyclyl, heterocylylalkyl, heteroaryl orheteroarylalkyl, and where each of the above substituents isunsubstituted unless otherwise indicated.

“Alkoxy” refers to a radical of the formula —OR_(a) where R_(a) is analkyl radical as defined above containing one to twelve carbon atoms.The alkyl part of the alkoxy radical may be optionally substituted asdefined above for an alkyl radical.

“Alkoxyalkyl” refers to a radical of the formula —R_(a)—O—R_(a) whereeach R_(a) is independently an alkyl radical as defined above. Theoxygen atom may be bonded to any carbon in either alkyl radical. Eachalkyl part of the alkoxyalkyl radical may be optionally substituted asdefined above for an alkyl group.

“Aryl” refers to aromatic monocyclic or multicyclic hydrocarbon ringsystem consisting only of hydrogen and carbon and containing from 6 to19 carbon atoms, where the ring system may be partially or fullysaturated. Aryl groups include, but are not limited to, groups such asfluorenyl, phenyl and naphthyl. Unless stated otherwise specifically inthe specification, the term “aryl” or the prefix “ar-” (such as in“aralkyl”) is meant to include aryl radicals optionally substituted byone or more substituents independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl,haloalkynyl, cyano, nitro, optionally substituted aryl, optionallysubstituted aralkyl, optionally substituted aralkenyl, optionallysubstituted aralkynyl, optionally substituted cycloalkyl, optionallysubstituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl,optionally substituted cycloalkylalkynyl, optionally substitutedheterocyclyl, optionally substituted heterocyclylalkyl, optionallysubstituted heterocyclylalkenyl, optionally substitutedheterocyclylalkynyl, optionally substituted heteroaryl, optionallysubstituted heteroarylalkyl, optionally substituted heteroarylalkenyl,optionally substituted heteroarylalkynyl, —R¹⁵—OR¹⁴, —R¹⁵—OC(O)—R¹⁴,—R¹⁵—N(R¹⁴)₂, —R¹⁵—C(O)R¹⁴, —R¹⁵—C(O)OR¹⁴, —R¹⁵—C(O)N(R¹⁴)₂,—R¹⁵—O—R¹⁶—C(O)N(R¹⁴)₂, —R¹⁵—N(R¹⁴)C(O)OR¹⁴, —R¹⁵—N(R¹⁴)C(O)R¹⁴,—R¹⁵—N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —R¹⁵—S(O)_(t)OR¹⁴ (where tis 1 or 2), —R¹⁵—S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and—R¹⁵—S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2), where each R¹⁴ isindependently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl,aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl orheteroarylalkyl, each R¹⁵ is independently a direct bond or a straightor branched alkylene or alkenylene chain, and R¹⁶ is a straight orbranched alkylene or alkenylene chain, and where each of the abovesubstituents is unsubstituted unless otherwise indicated.

“Aralkyl” refers to a radical of the formula —R_(a)R_(b) where R_(a) isan alkyl radical as defined above and R_(b) is one or more aryl radicalsas defined above, for example, benzyl, diphenylmethyl and the like. Thealkyl part of the aralkyl radical may be optionally substituted asdescribed above for an alkyl group. The aryl part of the aralkyl radicalmay be optionally substituted as described above for an aryl group.

“Aralkenyl” refers to a radical of the formula —R_(c)R_(b) where R_(c)is an alkenyl radical as defined above and R_(b) is one or more arylradicals as defined above. The aryl part of the aralkenyl radical may beoptionally substituted as described above for an aryl group. The alkenylpart of the aralkenyl radical may be optionally substituted as definedabove for an alkenyl group.

“Aralkynyl” refers to a radical of the formula —R_(d)R_(b) where R_(d)is an alkynyl radical as defined above and R_(b) is one or more arylradicals as defined above. The aryl part of the aralkynyl radical may beoptionally substituted as described above for an aryl group. The alkynylpart of the aralkynyl radical may be optionally substituted as definedabove for an alkynyl group.

“Aryloxy” refers to a radical of the formula —OR_(b) where R_(b) is anaryl group as defined above. The aryl part of the aryloxy radical may beoptionally substituted as defined above.

“Aralkyloxy” refers to a radical of the formula —OR_(b) where R_(b) isan aralkyl group as defined above. The aralkyl part of the aralkyloxyradical may be optionally substituted as defined above.

“Cycloalkyl” refers to a stable non-aromatic monocyclic or polycyclichydrocarbon radical consisting solely of carbon and hydrogen atoms,which may include fused or bridged ring systems, having from three tofifteen carbon atoms, preferably having from three to ten carbon atoms,and which is saturated or unsaturated and attached to the rest of themolecule by a single bond. Monocyclic radicals include, for example,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, andcyclooctyl. Polycyclic radicals include, for example, adamantine,norbornane, norbornene, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl,and the like. Unless otherwise stated specifically in the specification,the term “cycloalkyl” is meant to include cycloalkyl radicals which areoptionally substituted by one or more substituents independentlyselected from the group consisting of alkyl, alkenyl, alkynyl, halo,haloalkyl, haloalkenyl, haloalkynyl, oxo, thioxo, cyano, nitro,optionally substituted aryl, optionally substituted aralkyl, optionallysubstituted aralkenyl, optionally substituted aralkynyl, optionallysubstituted cycloalkyl, optionally substituted cycloalkylalkyl,optionally substituted cycloalkylalkenyl, optionally substitutedcycloalkylalkynyl, optionally substituted heterocyclyl, optionallysubstituted heterocyclylalkyl, optionally substitutedheterocyclylalkenyl, optionally substituted heterocyclylalkynyl,optionally substituted heteroaryl, optionally substitutedheteroarylalkyl, optionally substituted heteroarylalkenyl, optionallysubstituted heteroarylalkynyl, —R¹⁵—OR¹⁴, —R¹⁵—OC(O)—R¹⁴, —R¹⁵—N(R¹⁴)₂,—R¹⁵—C(O)R¹⁴, —R¹⁵—C(O)OR¹⁴, —R¹⁵—C(O)N(R¹⁴)₂, —R¹⁵—N(R¹⁴)C(O)OR¹⁴,—R¹⁵—N(R¹⁴)C(O)R¹⁴, —R¹⁵—N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2),—R¹⁵—S(O)_(t)OR¹⁴ (where t is 1 or 2), —R¹⁵—S(O)_(p)R¹⁴ (where p is 0, 1or 2), and —R¹⁵—S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2), where each R¹⁴ isindependently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl,aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl orheteroarylalkyl, and each R¹⁵ is independently a direct bond or astraight or branched alkylene or alkenylene chain, and where each of theabove substituents is unsubstituted unless otherwise indicated.

“Cycloalkylalkyl” refers to a radical of the formula —R_(a)R_(e) whereR_(a) is an alkyl radical as defined above and R_(e) is a cycloalkylradical as defined above. The alkyl radical and the cycloalkyl radicalmay be optionally substituted as defined above.

“Cycloalkylalkenyl” refers to a radical of the formula —R_(c)R_(e) whereR_(c) is an alkenyl radical as defined above and R_(e) is a cycloalkylradical as defined above. The alkenyl radical and the cycloalkyl radicalmay be optionally substituted as defined above.

“Cycloalkylalkynyl” refers to a radical of the formula —R_(d)R_(e) whereR_(d) is an alkynyl radical as defined above and R_(e) is a cycloalkylradical as defined above. The alkynyl radical and the cycloalkyl radicalmay be optionally substituted as defined above.

“Halo” refers to bromo, chloro, fluoro or iodo.

“Haloalkyl” refers to an alkyl radical, as defined above, that issubstituted by one or more halo radicals, as defined above, for example,trifluoromethyl, difluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl,1-fluoromethyl-2-fluoroethyl, 3-bromo-2-fluoropropyl,1-bromomethyl-2-bromoethyl, and the like. The alkyl part of thehaloalkyl radical may be optionally substituted as defined above for analkyl group.

“Haloalkenyl” refers to an alkenyl radical, as defined above, that issubstituted by one or more halo radicals, as defined above. The alkenylpart of the haloalkyl radical may be optionally substituted as definedabove for an alkenyl group.

“Haloalkynyl” refers to an alkynyl radical, as defined above, that issubstituted by one or more halo radicals, as defined above. The alkynylpart of the haloalkyl radical may be optionally substituted as definedabove for an alkynyl group.

“Heterocyclyl” refers to a stable 3- to 18-membered non-aromatic ringradical which consists of one to twelve carbon atoms and from one to sixheteroatoms selected from the group consisting of nitrogen, oxygen andsulfur. Unless stated otherwise specifically in the specification, theheterocyclyl radical may be a monocyclic, bicyclic, tricyclic ortetracyclic ring system, which may include fused or bridged ringsystems; and the nitrogen, carbon or sulfur atoms in the heterocyclylradical may be optionally oxidized; the nitrogen atom may be optionallyquaternized; and the heterocyclyl radical may be partially or fullysaturated. Examples of such heterocyclyl radicals include, but are notlimited to, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl,imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl,morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl,2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl,piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, thiazolidinyl,tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl,thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl.Unless stated otherwise specifically in the specification, the term“heterocyclyl” is meant to include heterocyclyl radicals as definedabove which are optionally substituted by one or more substituentsselected from the group consisting of alkyl, alkenyl, alkynyl, halo,haloalkyl, haloalkenyl, haloalkynyl, oxo, thioxo, cyano, nitro,optionally substituted aryl, optionally substituted aralkyl, optionallysubstituted aralkenyl, optionally substituted aralkynyl, optionallysubstituted cycloalkyl, optionally substituted cycloalkylalkyl,optionally substituted cycloalkylalkenyl, optionally substitutedcycloalkylalkynyl, optionally substituted heterocyclyl, optionallysubstituted heterocyclylalkyl, optionally substitutedheterocyclylalkenyl, optionally substituted heterocyclylalkynyl,optionally substituted heteroaryl, optionally substitutedheteroarylalkyl, optionally substituted heteroarylalkenyl, optionallysubstituted heteroarylalkynyl, —R¹⁵—OR¹⁴, —R¹⁵—OC(O)—R¹⁴, —R¹⁵—N(R¹⁴)₂,—R¹⁵—C(O)R¹⁴, —R¹⁵—C(O)OR¹⁴, —R¹⁵—C(O)N(R¹⁴)₂, —R¹⁵—N(R¹⁴)C(O)OR¹⁴,—R¹⁵—N(R¹⁴)C(O)R¹⁴, —R¹⁵—N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2),—R¹⁵—S(O)_(t)OR¹⁴ (where t is 1 or 2), —R¹⁵—S(O)_(p)R¹⁴ (where p is 0, 1or 2), and —R¹⁵—S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2), where each R¹⁴ isindependently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl,aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl orheteroarylalkyl, and each R¹⁵ is independently a direct bond or astraight or branched alkylene or alkenylene chain, and where each of theabove substituents is unsubstituted unless otherwise indicated.

“N-heterocyclyl” refers to a heterocyclyl radical as defined abovecontaining at least one nitrogen and where the point of attachment ofthe heterocyclyl radical to the rest of the molecule is through anitrogen atom in the heterocyclyl radical. An N-heterocyclyl radical maybe optionally substituted as described above for heterocyclyl radicals.

“Heterocyclylalkyl” refers to a radical of the formula —R_(a)R_(f) whereR_(a) is an alkyl radical as defined above and R_(f) is a heterocyclylradical as defined above, and if the heterocyclyl is anitrogen-containing heterocyclyl, the heterocyclyl may be attached tothe alkyl radical at the nitrogen atom. The alkyl part of theheterocyclylalkyl radical may be optionally substituted as defined abovefor an alkyl group. The heterocyclyl part of the heterocyclylalkylradical may be optionally substituted as defined above for aheterocyclyl group.

“Heterocyclylalkenyl” refers to a radical of the formula —R_(c)R_(f)where R_(c) is an alkenyl radical as defined above and R_(f) is aheterocyclyl radical as defined above, and if the heterocyclyl is anitrogen-containing heterocyclyl, the heterocyclyl may be attached tothe alkenyl radical at the nitrogen atom. The alkenyl part of theheterocyclylalkenyl radical may be optionally substituted as definedabove for an alkenyl group. The heterocyclyl part of theheterocyclylalkenyl radical may be optionally substituted as definedabove for a heterocyclyl group.

“Heterocyclylalkynyl” refers to a radical of the formula —R_(d)R_(f)where R_(d) is an alkynyl radical as defined above and R_(f) is aheterocyclyl radical as defined above, and if the heterocyclyl is anitrogen-containing heterocyclyl, the heterocyclyl may be attached tothe alkynyl radical at the nitrogen atom. The alkynyl part of theheterocyclylalkynyl radical may be optionally substituted as definedabove for an alkynyl group. The heterocyclyl part of theheterocyclylalkynyl radical may be optionally substituted as definedabove for a heterocyclyl group.

“Heteroaryl” refers to a 3- to 18-membered partially or fully aromaticring radical which consists of one to thirteen carbon atoms and from oneto six heteroatoms selected from the group consisting of nitrogen,oxygen and sulfur. For purposes of this invention, the heteroarylradical may be a monocyclic, bicyclic, tricyclic or tetracyclic ringsystem, which may include fused or bridged ring systems; and thenitrogen, carbon or sulfur atoms in the heteroaryl radical may beoptionally oxidized; the nitrogen atom may be optionally quaternized.Examples include, but are not limited to, azepinyl, acridinyl,benzimidazolyl, benzthiazolyl, benzindolyl, 1,3-benzodioxolyl,benzofuranyl, benzooxazolyl, benzothiazolyl, benzothiadiazolyl,benzo[b][1,4]dioxepinyl, benzo[b][1,4]oxazinyl, 1,4-benzodioxanyl,benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl,benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl(benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl,carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl,furanonyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl,isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl,isoxazolyl, naphthyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl,oxazolyl, oxiranyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl,phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl,pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl,quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl,tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl,triazinyl, and thiophenyl (i.e. thienyl). Unless stated otherwisespecifically in the specification, the term “heteroaryl” is meant toinclude heteroaryl radicals as defined above which are optionallysubstituted by one or more substituents selected from the groupconsisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl,haloalkynyl, oxo, thioxo, cyano, nitro, optionally substituted aryl,optionally substituted aralkyl, optionally substituted aralkenyl,optionally substituted aralkynyl, optionally substituted cycloalkyl,optionally substituted cycloalkylalkyl, optionally substitutedcycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionallysubstituted heterocyclyl, optionally substituted heterocyclylalkyl,optionally substituted heterocyclylalkenyl, optionally substitutedheterocyclylalkynyl, optionally substituted heteroaryl, optionallysubstituted heteroarylalkyl, optionally substituted heteroarylalkenyl,optionally substituted heteroarylalkynyl, —R¹⁵—OR¹⁴, —R¹⁵—OC(O)—R¹⁴,—R¹⁵—N(R¹⁴)₂, —R¹⁵—C(O)R¹⁴, —R¹⁵—C(O)OR¹⁴, —R¹⁵—C(O)N(R¹⁴)₂,—R¹⁵—N(R¹⁴)C(O)OR¹⁴, —R¹⁵—N(R¹⁴)C(O)R¹⁴, —R¹⁵—N(R¹⁴)S(O)R¹⁴ (where t is1 or 2), —R¹⁵—S(O)_(t)OR¹⁴ (where t is 1 or 2), —R¹⁵—S(O)_(p)R¹⁴ (wherep is 0, 1 or 2), and —R¹⁵—S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2), whereeach R¹⁴ is independently hydrogen, alkyl, haloalkyl, cycloalkyl,cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl,heteroaryl or heteroarylalkyl, and each R¹⁵ is independently a directbond or a straight or branched alkylene or alkenylene chain, and whereeach of the above substituents is unsubstituted unless otherwiseindicated.

“N-heteroaryl” refers to a heteroaryl radical as defined abovecontaining at least one nitrogen and where the point of attachment ofthe heteroaryl radical to the rest of the molecule is through a nitrogenatom in the heteroaryl radical. An N-heteroaryl radical may beoptionally substituted as described above for heteroaryl radicals.

“Heteroarylalkyl” refers to a radical of the formula —R_(a)R_(g) whereR_(a) is an alkyl radical as defined above and R_(g) is a heteroarylradical as defined above. The heteroaryl part of the heteroarylalkylradical may be optionally substituted as defined above for a heteroarylgroup. The alkyl part of the heteroarylalkyl radical may be optionallysubstituted as defined above for an alkyl group.

“Heteroarylalkenyl” refers to a radical of the formula —R_(c)R_(g) whereR_(c) is an alkenyl radical as defined above and R_(g) is a heteroarylradical as defined above. The heteroaryl part of the heteroarylalkenylradical may be optionally substituted as defined above for a heteroarylgroup. The alkenyl part of the heteroarylalkenyl radical may beoptionally substituted as defined above for an alkenyl group.

“Heteroarylalkynyl” refers to a radical of the formula —R_(d)R_(g) whereR_(d) is an alkynyl radical as defined above and R_(g) is a heteroarylradical as defined above. The heteroaryl part of the heteroarylalkynylradical may be optionally substituted as defined above for a heteroarylgroup. The alkynyl part of the heteroarylalkynyl radical may beoptionally substituted as defined above for an alkynyl group.

“Hydroxyalkyl” refers to an alkyl radical as defined above which issubstituted by one or more hydroxy groups (—OH).

“Hydroxyalkenyl” refers to an alkenyl radical as defined above which issubstituted by one or more hydroxy groups (—OH).

“Hydroxyalkenyl” refers to an alkynyl radical as defined above which issubstituted by one or more hydroxy groups (—OH).

Certain chemical groups named herein may be preceded by a shorthandnotation indicating the total number of carbon atoms that are to befound in the indicated chemical group. For example; C₇-C₁₂alkyldescribes an alkyl group, as defined below, having a total of 7 to 12carbon atoms, and C₄-C₁₂cycloalkylalkyl describes a cycloalkylalkylgroup, as defined below, having a total of 4 to 12 carbon atoms. Thetotal number of carbons in the shorthand notation does not includecarbons that may exist in substituents of the group described.

“Prodrugs” is meant to indicate a compound that may be converted underphysiological conditions or by solvolysis to a biologically activecompound of the invention. Thus, the term “prodrug” refers to aprecursor of a compound of the invention that is pharmaceuticallyacceptable. A prodrug may be inactive when administered to a subject inneed thereof, but is converted in vivo to an active compound of theinvention for example, by hydrolysis in blood. The prodrug compoundoften offers advantages of solubility, tissue compatibility or delayedrelease in a mammalian organism (see, Bundgard, H., Design of Prodrugs(1985), pp. 7-9, 21-24 (Elsevier, Amsterdam).

A discussion of prodrugs is provided in Higuchi, T., et al., “Pro-drugsas Novel Delivery Systems,” A.C.S. Symposium Series, Vol. 14, and inBioreversible Carriers in Drug Design, ed. Edward B. Roche, AmericanPharmaceutical Association and Pergamon Press, 1987, both of which areincorporated in full by reference herein.

The term “prodrug” is also meant to include any covalently bondedcarriers, which release the active compound of the invention in vivowhen such prodrug is administered to a mammalian subject. Prodrugs of acompound of the invention may be prepared by modifying functional groupspresent in the compound of the invention in such a way that themodifications are cleaved, either in routine manipulation or in vivo, tothe parent compound of the invention. Prodrugs include compounds of theinvention wherein a hydroxy, amino or mercapto group is bonded to anygroup that, when the prodrug of the compound of the invention isadministered to a mammalian subject, cleaves to form a free hydroxy,free amino or free mercapto group, respectively. Examples of prodrugsinclude, but are not limited to, acetate, formate and benzoatederivatives of alcohol or amine functional groups in the compounds ofthe invention and the like.

“Stable compound” and “stable structure” are meant to indicate acompound that is sufficiently robust to survive isolation to a usefuldegree of purity from a reaction mixture, and formulation into anefficacious therapeutic agent.

“Mammal” includes humans and domestic animals, such as cats, dogs,swine, cattle, sheep, goats, horses, rabbits, and the like. Preferably,for purposes of this invention, the mammal is a human.

“Optional” or “optionally” means that the subsequently described eventof circumstances may or may not occur, and that the description includesinstances where said event or circumstance occurs and instances in whichit does not. For example, “optionally substituted aryl” means that thearyl radical may or may not be substituted and that the descriptionincludes both substituted aryl radicals and aryl radicals having nosubstitution.

“Pharmaceutically acceptable excipient” includes without limitation anyadjuvant, carrier, excipient, glidant, sweetening agent, diluent,preservative, dye/colorant, flavor enhancer, surfactant, wetting agent,dispersing agent, suspending agent, stabilizer, isotonic agent, solvent,or emulsifier which has been approved by the United States Food and DrugAdministration as being acceptable for use in humans or domesticanimals.

“Pharmaceutically acceptable salt” includes both acid and base additionsalts.

“Pharmaceutically acceptable acid addition salt” refers to those saltswhich retain the biological effectiveness and properties of the freebases, which are not biologically or otherwise undesirable, and whichare formed with inorganic acids such as, but not limited to,hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid,phosphoric acid and the like, and organic acids such as, but not limitedto, acetic acid, 2,2-dichloroacetic acid, adipic acid, alginic acid,ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid,4-acetamidobenzoic acid, camphoric acid, camphor-10-sulfonic acid,capric acid, caproic acid, caprylic acid, carbonic acid, cinnamic acid,citric acid, cyclamic acid, dodecylsulfonic acid, ethane-1,2-disulfonicacid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, formic acid,fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid,gluconic acid, glucuronic acid, glutamic acid, glutaric acid,2-oxo-glutaric acid, glycerophosphoric acid, glycolic acid, hippuricacid, isobutyric acid, lactic acid, lactobionic acid, lauric acid,maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonicacid, mucic acid, naphthalene-1,5-disulfonic acid,naphthalene-2-sulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid,oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid,propionic acid, pyroglutamic acid, pyruvic acid, salicylic acid,4-aminosalicylic acid, sebacic acid, stearic acid, succinic acid,tartaric acid, thiocyanic acid, p-toluenesulfonic acid, trifluoroaceticacid, undecylenic acid, and the like.

“Pharmaceutically acceptable base addition salt” refers to those saltswhich retain the biological effectiveness and properties of the freeacids, which are not biologically or otherwise undesirable. These saltsare prepared from addition of an inorganic base or an organic base tothe free acid. Salts derived from inorganic bases include, but are notlimited to, the sodium, potassium, lithium, ammonium, calcium,magnesium, iron, zinc, copper, manganese, aluminum salts and the like.Preferred inorganic salts are the ammonium, sodium, potassium, calcium,and magnesium salts. Salts derived from organic bases include, but arenot limited to, salts of primary, secondary, and tertiary amines,substituted amines including naturally occurring substituted amines,cyclic amines and basic ion exchange resins, such as ammonia,isopropylamine, trimethylamine, diethylamine, triethylamine,tripropylamine, diethanolamine, ethanolamine, 2-dimethylaminoethanol,2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine,caffeine, procaine, hydrabamine, choline, betaine, benethamine,benzathine, ethylenediamine, glucosamine, methylglucamine, theobromine,triethanolamine, tromethamine, purines, piperazine, piperidine,N-ethylpiperidine, polyamine resins and the like. Particularly preferredorganic bases are isopropylamine, diethylamine, ethanolamine,trimethylamine, dicyclohexylamine, choline and caffeine.

Often crystallizations produce a solvate of the compound of theinvention. As used herein, the term “solvate” refers to an aggregatethat comprises one or more molecules of a compound of the invention withone or more molecules of solvent. The solvent may be water, in whichcase the solvate may be a hydrate. Alternatively, the solvent may be anorganic solvent. Thus, the compounds of the present invention may existas a hydrate, including a monohydrate, dihydrate, hemihydrate,sesquihydrate, trihydrate, tetrahydrate and the like, as well as thecorresponding solvated forms. The compound of the invention may be truesolvates, while in other cases, the compound of the invention may merelyretain adventitious water or be a mixture of water plus someadventitious solvent.

A “pharmaceutical composition” refers to a formulation of a compound ofthe invention and a medium generally accepted in the art for thedelivery of the biologically active compound to mammals, for example,humans. Such a medium includes all pharmaceutically acceptable carriers,diluents or excipients therefor.

“Therapeutically effective amount” refers to that amount of a compoundof the invention which, when administered to a mammal, preferably ahuman, is sufficient to effect treatment, as defined below, of a diseaseor condition of interest in the mammal, preferably a human. The amountof a compound of the invention which constitutes a “therapeuticallyeffective amount” will vary depending on the compound, the disease orcondition and its severity, and the age of the mammal to be treated, butcan be determined routinely by one of ordinary skill in the art havingregard to his own knowledge and to this disclosure.

“Treating” or “treatment” as used herein covers the treatment of thedisease or condition of interest in a mammal, preferably a human, havingthe disease or condition of interest, and includes:

(i) preventing the disease or condition from occurring in a mammal, inparticular, when such mammal is predisposed to the condition but has notyet been diagnosed as having it;

(ii) inhibiting the disease or condition, i.e., arresting itsdevelopment;

(iii) relieving the disease or condition, i.e., causing regression ofthe disease or condition; or

(iv) stabilizing the disease or condition.

As used herein, the terms “disease” and “condition” may be usedinterchangeably or may be different in that the particular malady orcondition may not have a known causative agent (so that etiology has notyet been worked out) and it is therefore not yet recognized as a diseasebut only as an undesirable condition or syndrome, wherein a more or lessspecific set of symptoms have been identified by clinicians.

The compounds of the invention, or their pharmaceutically acceptablesalts may contain one or more asymmetric centres and may thus give riseto enantiomers, diastereomers, and other stereoisomeric forms that maybe defined, in terms of absolute stereochemistry, as (R)- or (S)- or, as(D)- or (L)- for amino acids. The present invention is meant to includeall such possible isomers, as well as their racemic and optically pureforms. Optically active (+) and (−), (R)- and (S)-, or (D)- and(L)-isomers may be prepared using chiral synthons or chiral reagents, orresolved using conventional techniques, such as HPLC using a chiralcolumn. When the compounds described herein contain olefinic doublebonds or other centres of geometric asymmetry, and unless specifiedotherwise, it is intended that the compounds include both E and Zgeometric isomers. Likewise, all tautomeric forms are also intended tobe included.

A “stereoisomer” refers to a compound made up of the same atoms bondedby the same bonds but having different three-dimensional structures,which are not interchangeable. The present invention contemplatesvarious stereoisomers and mixtures thereof and includes “enantiomers”,which refers to two stereoisomers whose molecules are nonsuperimposeablemirror images of one another.

A “tautomer” refers to a proton shift from one atom of a molecule toanother atom of the same molecule. The present invention includestautomers of any said compounds.

“Atropisomers” are stereoisomers resulting from hindered rotation aboutsingle bonds where the barrier to rotation is high enough to allow forthe isolation of the conformers (Eliel, E. L.; Wilen, S. H.Stereochemistry of Organic Compounds; Wiley & Sons: New York, 1994;Chapter 14). Atropisomerism is significant because it introduces anelement of chirality in the absence of stereogenic atoms. The inventionis meant to encompass atropisomers, for example in cases of limitedrotation around the single bonds emanating from the core triazolestructure, atropisomers are also possible and are also specificallyincluded in the compounds and/or prodrugs of the invention.

The chemical naming protocol and structure diagrams used herein are amodified form of the I.U.P.A.C. nomenclature system wherein thecompounds of the invention are named herein as derivatives of thecentral core structure, i.e., the triazole structure. For complexchemical names employed herein, a substituent group is named before thegroup to which it attaches. For example, cyclopropylethyl comprises anethyl backbone with cyclopropyl substituent. In chemical structurediagrams, all bonds are identified, except for some carbon atoms, whichare assumed to be bonded to sufficient hydrogen atoms to complete thevalency.

The numbering system of the ring atoms in compounds of formula (Ia) and(Ib) is shown below:

For example, a compound of formula (Ia) wherein A is —C(O)—, R¹ isphenyl substituted at the 4-position by —R⁸—OR¹⁰ (where R⁸ is a directbond and R¹⁰ is 2-pyrrolidin-1-ylethyl); R², R⁴ and R⁵ are each hydrogenand R³ is 1H-indol-5-yl; i.e., a compound of the following formula:

is named herein as5-amino-1-(1H-indol-5-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole.

EMBODIMENTS OF THE INVENTION

One embodiment of the various aspects of the invention set forth abovein the Summary of the Invention are compounds of formula (Ia):

-   wherein:-   A is —C(O)—;-   R¹ is one of the following:    -   a) aryl substituted with one or more substituents selected from        the group consisting of halo, haloalkyl, alkyl, optionally        substituted heteroaryl, optionally substituted heterocyclyl,        —R⁸—OR¹⁰, —R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—CN,        —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶        (where p is 0, 1 or 2), —R⁸—O—R⁹—N(R⁶)R⁷,        —R⁶—O—R⁹—C(NR¹¹)N(R¹¹)H, and —R⁸—N(R⁶)C(O)R¹⁰; or    -   b) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, halo,        oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁶)R⁷; or    -   c) heterocyclyl optionally substituted with one or more        substituents selected from the group consisting of halo,        haloalkyl, alkyl, oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷,        —R⁸—S(O)_(p)R¹⁰ (where p is 0, 1 or 2) and —R⁸—N(R⁶)R⁷;    -   d) heterocyclylalkyl optionally substituted with one or more        substitutents selected from the group consisting of halo,        haloalkyl, alkyl, optionally substituted aryl, optionally        substituted aralkyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and        —R⁸—N(R⁶)R⁷; or    -   e) cycloalkyl optionally substituted with one or more        substituents selected from the group consisting of halo,        haloalkyl, alkyl, oxo, —R⁶—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷,        —R⁸—S(O)_(p)R¹⁰ (where p is 0, 1 or 2) and —R⁸—N(R⁶)R⁷;-   R² is hydrogen, alkyl or —C(O)R¹⁰;-   R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is one of the following:    -   a) alkyl optionally substituted with one or more substituents        selected from the group consisting of halo, cyano, nitro, oxo,        thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,        —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,        —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t        is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and        —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is        independently hydrogen, alkyl, haloalkyl, cycloalkyl,        cycloalkylalkyl, aryl (optionally substituted with one or more        halo groups), aralkyl, heterocyclyl, heterocylylalkyl,        heteroaryl or heteroarylalkyl;    -   b) cycloalkyl optionally substituted with one or more        substituents selected from the group consisting of —R⁸—OR¹⁰,        alkyl, halo, haloalkyl, aryl, and aralkyl;    -   c) aryl substituted with one or more substituents selected from        the group consisting of alkyl, halo, haloalkyl, nitro,        cycloalkyl, cycloalkylalkyl, optionally substituted aryl,        optionally substituted heteroaryl, optionally substituted        heterocyclyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,        —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is        0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,        —R⁸—N(R⁶)C(O)R¹⁰, —R⁸—N(R⁶)C(O)OR¹⁰ and —R⁸—CN;    -   d) aralkyl, wherein:        -   (1) the alkyl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of halo, cyano, nitro, oxo, thioxo,            trimethylsilanyl, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴, —C(O)OR¹⁴,            —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,            —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where            t is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and            —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is            independently hydrogen, alkyl, haloalkyl, cycloalkyl,            cycloalkylalkyl, aryl (optionally substituted with one or            more halo groups), aralkyl, heterocyclyl, heterocylylalkyl,            heteroaryl or heteroarylalkyl; and        -   (2) the aryl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of alkyl, alkenyl, alkynyl, halo,            haloalkyl, haloalkenyl, haloalkynyl, cyano, nitro, aryl,            aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl,            cycloalkylalkenyl, cycloalkylalkynyl, heterocyclyl,            heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl,            heteroaryl, heteroarylalkyl, heteroarylalkenyl,            heteroarylalkynyl, —R¹⁵—OR¹⁴, —R¹⁵—OC(O)—R¹⁴, —R¹⁵—N(R¹⁴)₂,            —R¹⁵—C(O)R¹⁴, —R¹⁵—C(O)OR¹⁴, —R¹⁵—C(O)N(R¹⁴)₂,            —R¹⁵—O—R¹⁶—C(O)N(R¹⁴)₂, —R¹⁵—N(R¹⁴)C(O)OR¹⁴,            —R¹⁵—N(R¹⁴)C(O)R¹⁴, —R¹⁵—N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or            2), —R¹⁵—S(O)_(t)OR¹⁴ (where t is 1 or 2), —R¹⁵—S(O)_(p)R¹⁴            (where p is 0, 1 or 2), and —R¹⁵—S(O)_(t)N(R¹⁴)₂ (where t is            1 or 2), where each R¹⁴ is independently hydrogen, alkyl,            haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl,            heterocyclyl, heterocyclylalkyl, heteroaryl or            heteroarylalkyl, each R¹⁵ is independently a direct bond or            a straight or branched alkylene or alkenylene chain, and R¹⁶            is a straight or branched alkylene or alkenylene chain;    -   e) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, oxo,        and —R⁹—OR¹⁰; or    -   f) heteroarylalkenyl where the heteroaryl part of the        heteroarylakyl radical is optionally substituted with one or        more substituents selected from the group consisting of alkyl,        halo, haloalkyl, aryl and aralkyl;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is one of the following:    -   a) aryl substituted with one or more substituents selected from        the group consisting of halo, haloalkyl, alkyl, optionally        substituted heteroaryl, optionally substituted heterocyclyl,        —R⁸—OR¹⁰, —R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R³—OR¹⁰, —R⁸—O—R⁹—CN,        —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶        (where p is 0, 1 or 2), —R⁸—O—R⁹—N(R⁶)R⁷,        —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and —R⁸—N(R⁶)C(O)R¹⁰; or    -   b) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, halo,        oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹³, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁶)R⁷;    -   c) heterocyclyl optionally substituted with one or more        substituents selected from the group consisting of halo,        haloalkyl, alkyl, oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰,        —R^(B)—C(O)N(R⁶)R⁷, —R³—S(O)_(p)R¹⁰ (where p is 0, 1 or 2) and        —R⁸—N(R⁶)R⁷; or    -   d) heterocyclylalkyl optionally substituted with one or more        substitutents selected from the group consisting of halo,        haloalkyl, alkyl, optionally substituted aryl, optionally        substituted aralkyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and        —R⁸—N(R⁶)R⁷;-   R² is hydrogen, alkyl or —C(O)R¹⁰;-   R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is one of the following:    -   a) alkyl optionally substituted with one or more substituents        selected from the group consisting of halo, cyano, nitro, oxo,        thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,        —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,        —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t        is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and        —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is        independently hydrogen, alkyl, haloalkyl, cycloalkyl,        cycloalkylalkyl, aryl (optionally substituted with one or more        halo groups), aralkyl, heterocyclyl, heterocylylalkyl,        heteroaryl or heteroarylalkyl;    -   b) cycloalkyl optionally substituted with one or more        substituents selected from the group consisting of —R⁸—OR¹⁰,        alkyl, halo, haloalkyl, aryl, and aralkyl;    -   c) aryl substituted with one or more substituents selected from        the group consisting of alkyl, halo, haloalkyl, nitro,        cycloalkyl, cycloalkylalkyl, optionally substituted aryl,        optionally substituted heteroaryl, optionally substituted        heterocyclyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,        —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is        0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,        —R⁸—N(R⁶)C(O)R¹⁰, —R⁸—N(R⁶)C(O)OR¹⁰ and —R⁸—CN;    -   d) aralkyl, wherein:        -   (1) the alkyl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of halo, cyano, nitro, oxo, thioxo,            trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,            —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,            —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where            t is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and            —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is            independently hydrogen, alkyl, haloalkyl, cycloalkyl,            cycloalkylalkyl, aryl (optionally substituted with one or            more halo groups), aralkyl, heterocyclyl, heterocylylalkyl,            heteroaryl or heteroarylalkyl; and        -   (2) the aryl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of alkyl, alkenyl, alkynyl, halo,            haloalkyl, haloalkenyl, haloalkynyl, cyano, nitro, aryl,            aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl,            cycloalkylalkenyl, cycloalkylalkynyl, heterocyclyl,            heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl,            heteroaryl, heteroarylalkyl, heteroarylalkenyl,            heteroarylalkynyl, —R¹⁵—OR¹⁴, —R¹⁵—OC(O)—R¹⁴, —R¹⁵—N(R¹⁴)₂,            —R¹⁵—C(O)R¹⁴, —R¹⁵—C(O)OR¹⁴, —R¹⁵—C(O)N(R¹⁴)₂,            —R¹⁵—O—R¹⁶—C(O)N(R¹⁴)₂, —R¹⁵—N(R¹⁴)C(O)OR¹⁴,            —R¹⁵—N(R¹⁴)C(O)R¹⁴, —R¹⁵—N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or            2), —R¹⁵—S(O)_(t)OR¹⁴ (where t is 1 or 2), —R¹⁵—S(O)_(p)R¹⁴            (where p is 0, 1 or 2), and —R¹⁵—S(O)_(t)N(R¹⁴)₂ (where t is            1 or 2), where each R¹⁴ is independently hydrogen, alkyl,            haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl,            heterocyclyl, heterocyclylalkyl, heteroaryl or            heteroarylalkyl, each R¹⁵ is independently a direct bond or            a straight or branched alkylene or alkenylene chain, and R¹⁶            is a straight or branched alkylene or alkenylene chain;    -   e) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, oxo,        and —R⁸—OR¹⁰; or    -   f) heteroarylalkenyl where the heteroaryl part of the        heteroarylakyl radical is optionally substituted with one or        more substituents selected from the group consisting of alkyl,        halo, haloalkyl, aryl and aralkyl;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—NO₂, —R⁹—N(R¹⁰)₂, —R⁹—C(O)OR¹⁰ and    —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is aryl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—OR¹⁰, —R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁸—OR¹⁰, —R⁸—O—R⁹—CN,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁸—S(O)_(p)R⁶ (where    p is 0, 1 or 2), —R⁸—O—R⁸—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and    —R⁸—N(R⁶)C(O)R¹⁰;-   R², R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is one of the following:    -   a) alkyl optionally substituted with one or more substituents        selected from the group consisting of halo, cyano, nitro, oxo,        thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,        —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,        —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t        is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and        —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is        independently hydrogen, alkyl, haloalkyl, cycloalkyl,        cycloalkylalkyl, aryl (optionally substituted with one or more        halo groups), aralkyl, heterocyclyl, heterocylylalkyl,        heteroaryl or heteroarylalkyl;    -   b) cycloalkyl optionally substituted with one or more        substituents selected from the group consisting of —R⁸—OR¹⁰,        alkyl, halo, haloalkyl, aryl, and aralkyl;    -   c) aryl substituted with one or more substituents selected from        the group consisting of alkyl, halo, haloalkyl, nitro,        cycloalkyl, cycloalkylalkyl, optionally substituted aryl,        optionally substituted heteroaryl, optionally substituted        heterocyclyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,        —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is        0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,        —R⁸—N(R⁶)C(O)R¹⁰, —R⁸—N(R⁸)C(O)OR¹⁰ and —R⁶—CN;    -   d) aralkyl, wherein:        -   (1) the alkyl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of halo, cyano, nitro, oxo, thioxo,            trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,            —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,            —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where            t is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and            —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is            independently hydrogen, alkyl, haloalkyl, cycloalkyl,            cycloalkylalkyl, aryl (optionally substituted with one or            more halo groups), aralkyl, heterocyclyl, heterocylylalkyl,            heteroaryl or heteroarylalkyl; and        -   (2) the aryl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of alkyl, alkenyl, alkynyl, halo,            haloalkyl, haloalkenyl, haloalkynyl, cyano, nitro, aryl,            aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl,            cycloalkylalkenyl, cycloalkylalkynyl, heterocyclyl,            heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl,            heteroaryl, heteroarylalkyl, heteroarylalkenyl,            heteroarylalkynyl, —R¹⁵—OR¹⁴, —R¹⁵—OC(O)—R¹⁴, —R¹⁵—N(R¹⁴)₂,            —R¹⁵—C(O)R¹⁴, —R¹⁵—C(O)OR¹⁴, —R¹⁵—C(O)N(R¹⁴)₂,            —R¹⁵—O—R¹⁶—C(O)N(R¹⁴)₂, —R¹⁵—N(R¹⁴)C(O)OR¹⁴,            —R¹⁵—N(R¹⁴)C(O)R¹⁴, —R¹⁵—N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or            2), —R¹⁵—S(O)_(t)OR¹⁴ (where t is 1 or 2), —R¹⁵—S(O)_(p)R¹⁴            (where p is 0, 1 or 2), and —R¹⁵—S(O)_(t)N(R¹⁴)₂ (where t is            1 or 2), where each R¹⁴ is independently hydrogen, alkyl,            haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl,            heterocyclyl, heterocyclylalkyl, heteroaryl or            heteroarylalkyl, each R¹⁵ is independently a direct bond or            a straight or branched alkylene or alkenylene chain, and R¹⁶            is a straight or branched alkylene or alkenylene chain;    -   e) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, oxo,        and —R⁸—OR¹⁰; or    -   f) heteroarylalkenyl where the heteroaryl part of the        heteroarylakyl radical is optionally substituted with one or        more substituents selected from the group consisting of alkyl,        halo, haloalkyl, aryl and aralkyl;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is aryl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—OR¹⁰, —R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—CN,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶ (where    p is 0, 1 or 2), —R⁸—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and    —R⁸—N(R⁶)C(O)R¹⁰;-   R², R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is cycloalkyl optionally substituted with —R⁸—OR¹⁰; or-   R³ is aryl substituted with one or more substituents selected from    the group consisting of alkyl, halo, haloalkyl, nitro, cycloalkyl,    cycloalkylalkyl, optionally substituted aryl, optionally substituted    heteroaryl, optionally substituted heterocyclyl, —R⁶—OR¹⁰,    —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷,    —S(O)_(p)R⁶ (where p is 0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1    or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰, —R⁸—N(R⁶)C(O)OR¹⁰ and —R⁸—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—OR¹⁰, —R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—CN,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁸)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁸ (where    p is 0, 1 or 2), —R⁸—O—R⁹—N(R⁸)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and    —R⁸—N(R⁸)C(O)R¹⁰;-   R², R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is cycloalkyl optionally substituted with —R⁸—OR¹⁰; or-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of alkyl, halo, haloalkyl, nitro, cycloalkyl,    cycloalkylalkyl, optionally substituted aryl, optionally substituted    heteroaryl, optionally substituted heterocyclyl, —R⁸—OR¹⁰,    —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷,    —S(O)_(p)R⁶ (where p is 0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1    or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰, —R⁸—N(R⁶)C(O)OR¹⁰, and —R⁸—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁸ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with one or two substituents selected from    the group consisting of halo, haloalkyl, alkyl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—OR¹⁰, —R⁸—O—R⁸—OR¹⁰, —R⁸—O—R⁸—O—R⁸—OR¹⁰, —R⁸—O—R⁸—CN,    —R⁸—O—R⁸—C(O)OR¹⁰, —R⁸—O—R⁸—C(O)N(R⁶)R⁷, —R⁸—O—R⁸—S(O)_(p)R⁶ (where    p is 0, 1 or 2), —R⁸—O—R⁸—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and    —R⁸—N(R⁶)C(O)R¹⁰;-   R², R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is cycloalkyl optionally substituted with —R⁸—OR¹⁰; or-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of alkyl, halo, haloalkyl, nitro, cycloalkyl,    cycloalkylalkyl, optionally substituted aryl, optionally substituted    heteroaryl, optionally substituted heterocyclyl, —R⁸—OR¹⁰,    —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁸—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷,    —S(O)_(p)R⁶ (where p is 0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1    or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰, —R⁸—N(R⁶)C(O)OR¹⁰ and —R⁸—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    substituted heterocyclyl, optionally substituted heterocyclylalkyl,    optionally substituted heteroaryl, optionally substituted    heteroarylalkyl, —R⁸—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁸—N(R¹⁰)₂,    —R⁸—C(O)OR¹⁰ and —R⁸—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, and an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, and optionally substituted heteroarylalkyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, —R⁸—OR¹⁰,    —R⁸—O—R⁹—OR¹⁰, and —R⁸—O—R⁹—O—R⁹—OR¹⁰;-   R², R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is cycloalkyl optionally substituted with —R⁸—OR¹⁰;-   or R³ is phenyl substituted with one or more substituents selected    from the group consisting of alkyl, halo, haloalkyl, nitro,    cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—OR¹³, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰,    —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0, 1 or 2),    —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰,    —R⁸—N(R⁶)C(O)OR¹⁰ and —R⁸—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    substituted heterocyclyl, optionally substituted heterocyclylalkyl,    optionally substituted heteroaryl, optionally substituted    heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, and an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, and optionally substituted heteroarylalkyl.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, —R⁸—OR¹⁰,    —R⁸—O—R⁹—OR¹⁰, and —R⁸—O—R⁹—O—R⁹—OR¹⁰;-   R², R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is cycloalkyl optionally substituted with —R⁸—OR¹⁰;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, and an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, and optionally substituted heteroarylalkyl.

Of this embodiment, a specific embodiment is a compound of formula (Ia)selected from the group consisting of:

-   5-amino-1-[2-(bicyclo[2.2.1]hept-5-ene)carbonyl]-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(methoxy)cyclohexyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-[2-(bicyclo[2.2.1]heptane)carbonyl]-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;    and-   5-amino-1-(bicyclo[2.2.1]heptan-2-yl)carbonyl-3-[4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, —R⁸—OR¹⁰,    —R⁸—O—R⁹—OR¹⁰, and —R⁸—O—R⁹—O—R⁹—OR¹⁰;-   R², R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of alkyl, halo, haloalkyl, nitro, cycloalkyl,    cycloalkylalkyl, optionally substituted aryl, optionally substituted    heteroaryl, optionally substituted heterocyclyl, —R⁸—OR¹⁰,    —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷,    —S(O)_(p)R⁶ (where p is 0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1    or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰, —R⁸—N(R⁶)C(O)OR¹⁰ and —R⁸—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    substituted heterocyclyl, optionally substituted heterocyclylalkyl,    optionally substituted heteroaryl, optionally substituted    heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, and an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, and optionally substituted heteroarylalkyl.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, —R⁸—OR¹⁰,    —R⁹—O—R⁹—OR¹⁰, and —R⁸—O—R⁹—O—R⁹—OR¹⁰;-   R², R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of alkyl, halo, haloalkyl, nitro, —R⁸—OR¹⁰,    —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷,    —S(O)_(p)R⁶ (where p is 0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1    or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰, —R⁸—N(R⁶)C(O)OR¹⁰ and —R⁸—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    substituted heterocyclyl, optionally substituted heterocyclylalkyl,    optionally substituted heteroaryl, optionally substituted    heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, and an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, and optionally substituted heteroarylalkyl.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with —R⁸—OR¹⁰ and optionally substituted    with halo or alkoxy, where R⁸ is a direct bond and R¹⁰ is selected    from the group consisting of 2-(pyrrolidin-1-yl)ethyl,    2-(piperidin-1-yl)ethyl, 2-(morpholin-4-yl)ethyl,    2-(1,3-dioxolan-2-yl)ethyl, 2-(thiomorpholin-4-yl)ethyl,    3-(pyrrolidin-1-yl)propyl, 2-(azepan-1-yl)ethyl,    2-(isoindolin-1-yl)ethyl, 2-(imidazol-1-yl)ethyl,    2-(pyrrolidin-2-on-1-yl)ethyl, and 2-(3-fluoropyrrolidin-1-yl)ethyl;-   R², R⁴ and R⁵ are each hydrogen or alkyl; and-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of alkyl, halo, haloalkyl, nitro, —R⁸—OR¹⁰,    C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R)R⁷,    —S(O)_(p)R⁶ (where p is 0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1    or 2), —R⁶—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰, —R⁸—N(R⁶)C(O)OR¹⁰ and —R⁸—CN,    where:    -   R⁶ and R⁷ are each independently selected from the group        consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl,        optionally substituted aryl, optionally substituted aralkyl,        optionally substituted cycloalkyl, optionally substituted        cycloalkylalkyl, optionally substituted heterocyclyl, optionally        substituted heterocyclylalkyl, optionally substituted        heteroaryl, optionally substituted heteroarylalkyl, —R⁹—OR¹⁰,        —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂, —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;    -   optionally, R⁶ and R⁷, together with the nitrogen to which they        are attached, form an optionally substituted N-heteroaryl or an        optionally substituted N-heterocyclyl;    -   each R⁸ is independently selected from the group consisting of a        direct bond, an optionally substituted straight or branched        alkylene chain, and an optionally substituted straight or        branched alkenylene chain;    -   each R⁹ is independently selected from the group consisting of        an optionally substituted straight or branched alkylene chain,        or an optionally substituted straight or branched alkenylene        chain; and    -   each R¹⁰ is independently selected from the group consisting of        hydrogen, alkyl, haloalkyl, optionally substituted aryl,        optionally substituted aralkyl, optionally substituted        cycloalkyl, optionally substituted cycloalkylalkyl, optionally        substituted heterocyclyl, optionally substituted        heterocyclylalkyl, optionally substituted heteroaryl, and        optionally substituted heteroarylalkyl.

Of this embodiment, a specific embodiment is a compound of formula (Ia)selected from the group consisting of:

-   5-amino-1-(3-(iso-propoxy)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(iso-propoxy)phenyl)carbonyl-3-[4-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(methyl)phenylcarbonyl-3-[3-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenylcarbonyl-3-[3-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-3-[3-[2-(1,3-dioxolan-2-yl)ethoxy]phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-[2-(1,3-dioxolan-2-yl)ethoxy]phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenylcarbonyl-3-[4-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenylcarbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1-(4-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propyl)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(methyl)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(methyl)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenylcarbonyl-3-[4-[2-(thiomorpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(methyl)phenylcarbonyl-3-[4-[2-(thiomorpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(cyclohexyl)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(methoxycarbonyl)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(methoxy)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3,4-(dimethoxy)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3,5-(dimethoxy)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(dimethylamino)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-methylphenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3,5-(dimethoxy)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-methylphenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1-(4-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(3-methoxyphenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(dimethylamino)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3,4-(dimethoxy)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1-(3-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1-(3-(trifluoromethoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1-(4-(trifluoromethoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-[3-(pyrrolidin-1-yl)propoxy]phenylamino]-1-(4-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-[3-(pyrrolidin-1-yl)propoxy]phenylamino]-1-(3-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-[3-(pyrrolidin-1-yl)propoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[4-[3-(pyrrolidin-1-yl)propoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(dimethylamino)phenyl)carbonyl-3-[4-[3-(pyrrolidin-1-yl)propoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butyl)phenyl)carbonyl-3-[4-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(phenoxy)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butoxycarbonylamino)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenyl][methyl]amino-1H-1,2,4-triazole;-   5-amino-1-[4-((tert-butoxycarbonyl)aminomethyl)phenyl]carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(methylamino)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(methylthio)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(2,6-difluorophenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butylcarbonylamino)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butyl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[3-fluoro-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[3-fluoro-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butyl)phenyl)carbonyl-3-[3-methoxy-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[3-methoxy-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[3-methoxy-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butyl)phenyl)carbonyl-3-[4-[2-(azepan-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-[2-(azepan-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-[2-(azepan-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-[2-(isoindolin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-[2-(isoindolin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-[4-(2-(morpholin-4-yl)ethoxy)phenyl]carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-[2-(pyrrolidin-2-on-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-[2-(pyrrolidin-2-on-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(tert-butoxy)phenyl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(dimethylamino)phenyl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-fluoro-4-methoxyphenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-[2-((S)-3-fluoropyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[4-[2-((S)-3-fluoropyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3,5-difluoro-4-methoxyphenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;    and-   5-amino-3-[3-chloro-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1-(3,5-dichlorophenyl)carbonyl-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, —R⁸—O—R⁶—OR¹⁰,    —R⁸—O—R⁹—O—R⁶—OR¹⁰, and —R⁸—OR¹⁰ (where R¹⁰ for —R⁸—OR¹⁰ is    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl, or    optionally substituted heteroaryl);-   R², R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of alkyl, halo, haloalkyl, nitro, —R⁸—OR¹⁰,    —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷,    —S(O)_(p)R⁶ (where p is 0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1    or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰, —R⁸—N(R⁶)C(O)OR¹⁰ and —R⁸—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    substituted heterocyclyl, optionally substituted heterocyclylalkyl,    optionally substituted heteroaryl, optionally substituted    heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁶—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, and an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, and optionally substituted heteroarylalkyl.

Of this embodiment, a specific embodiment is a compound of formula (Ia)selected from the group consisting of:

-   5-amino-3-[3-(benzyloxy)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(hydroxy)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-(benzyloxy)phenylamino]-1-(4-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-(hydroxy)phenylamino]-1-(4-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(hydroxy)phenylamino]-1-(2-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(hydroxy)phenylamino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-(benzyloxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(benzyloxy)phenylamino]-1-(3-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-(iso-propoxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(hydroxy)phenylamino]-1-4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(hydroxy)phenylamino]-1-(3-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(benzyloxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(cyclopentoxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-(hydroxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-(methoxy)phenylamino]-1H-1,2,4-triazole;-   5-amino-3-[4-(ethoxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[3-(methoxy)phenylamino]-1H-1,2,4-triazole;-   5-amino-3-[3-(iso-propoxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-(fluoro)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(fluoro)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(ethoxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[2-(fluoro)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-(methyl)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-(methoxy)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(methyl)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(methoxy)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[3-(2,2,2-trifluoroethoxy)phenylamino]-1H-1,2,4-triazole;-   5-amino-3-[2-(methoxy)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[2-(methyl)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[-[2-(hydroxyl)ethoxy]phenylamino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-(cyclopentoxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-(2,2,2-trifluoroethoxy)phenylamino]-1H-1,2,4-triazole;-   5-amino-3-[2-(hydroxyl)phenylamino]-1-(4-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(3-methylphenyl)carbonyl-3-[3-[(2-methoxyethoxy)methoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-3-(3-methoxymethoxy)phenylamino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(4-chlorophenyl)amino-1-(4-chlorophenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(4-bromophenyl)amino-1-(4-chlorophenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-(iso-propoxy)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-(iso-propoxy)phenylamino]-1-(3-(nitro)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(3-(hydroxy)phenyl)carbonyl-3-[4-(iso-propoxy)phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(chloro)phenyl)carbonyl-3-[4-(iso-propoxy)phenylamino]-1H-1,2,4-triazole;    and-   5-amino-3-[4-(iso-propoxy)phenylamino]-1-[4-[2-(piperidin-1-yl)ethoxy]phenyl)carbonyl-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, —R⁸—OR¹⁰,    —R⁸—O—R⁹—OR¹⁰, and —R⁸—O—R⁹—O—R⁹—OR¹⁰;-   R², R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of cycloalkyl, cycloalkylalkyl, optionally    substituted aryl, optionally substituted heteroaryl, and optionally    substituted heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, and an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, and optionally substituted heteroarylalkyl.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with —R⁸—OR¹⁰ and optionally substituted    with halo, alkyl or alkoxy, where R⁸ is a direct bond and R¹⁰ is    selected from the group consisting of 2-(pyrrolidin-1-yl)ethyl,    2-(piperidin-1-yl)ethyl, 2-(morpholin-4-yl)ethyl,    2-(1,3-dioxolan-2-yl)ethyl, 2-(thiomorpholin-4-yl)ethyl,    3-(pyrrolidin-1-yl)propyl, 2-(azepan-1-yl)ethyl,    2-(isoindolin-1-yl)ethyl, 2-(imidazol-1-yl)ethyl,    2-(pyrrolidin-2-on-1-yl)ethyl, and 2-(3-fluoropyrrolidin-1-yl)ethyl;-   R², R⁴ and R⁵ are each hydrogen or alkyl; and-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of cycloalkyl, cycloalkylalkyl, optionally    substituted aryl, optionally substituted heteroaryl, and optionally    substituted heterocyclyl.

Of this embodiment, a specific embodiment is a compound of formula (Ia)selected from the group consisting of:

-   5-amino-3-[4-[2-(pyrrolidin-1-yl)ethoxy]-3-fluorophenyl]amino-1-[4-(morpholin-4-yl)phenyl]carbonyl-1H-1,2,4-triazole-   5-amino-1-(4-(imidazol-1-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(phenyl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(1,2,3-thiadiazol-4-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(pyrrol-1-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(1,2,3-thiadiazol-4-yl)phenyl)carbonyl-3-[3-fluoro-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(thiazol-2-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(thien-2-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(thien-2-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(thien-3-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(1,2,3-thiadiazol-4-yl)phenyl)carbonyl-3-[3-methoxy-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(1,2,3-thiadiazol-4-yl)phenyl)carbonyl-3-[4-[2-(azepan-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(morpholin-4-yl)phenyl)carbonyl-3-[4-[2-(isoindolin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(morpholin-4-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(1,2,3-thiadiazol-4-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-2-on-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(morpholin-4-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-2-on-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(morpholin-4-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-2-on-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(morpholin-4-yl)phenyl)carbonyl-3-[3-methoxy-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(morpholin-4-yl)phenyl)carbonyl-3-[3-methoxy-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(morpholin-4-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(4-methylpiperazin-1-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(1,1-dioxo-thiomorpholin-4-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;    and-   5-amino-1-(4-(piperidin-1-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with optionally substituted heteroaryl or    optionally substituted heterocyclyl;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of alkyl, halo, haloalkyl, nitro, cycloalkyl,    cycloalkylalkyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0,    1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,    —R⁸—N(R⁶)C(O)R¹⁰, and —R⁸—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    substituted heterocyclyl, optionally substituted heterocyclylalkyl,    optionally substituted heteroaryl, optionally substituted    heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, and an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, and optionally substituted heteroarylalkyl.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with optionally substituted heteroaryl or    optionally substituted heterocyclyl;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of alkyl, halo, haloalkyl, cycloalkyl, and    cycloalkylalkyl.

Of this embodiment, a specific embodiment is a compound of formula (Ia)selected from the group consisting of:

-   5-amino-1-(4-(iso-propyl)phenyl)carbonyl-3-(4-(morpholin-4-yl)phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(methyl)phenyl)carbonyl-3-(4-(morpholin-4-yl)phenylamino)-1H-1,2,4-triazole;-   5-amino-1-(3-(chloro)phenyl)carbonyl-3-(4-(morpholin-4-yl)phenylamino)-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butyl)phenyl)carbonyl-3-[3-(1,3-oxazol-5-yl)phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butyl)phenyl)carbonyl-3-[4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole;    and-   5-amino-1-(4-(methyl)phenyl)carbonyl-3-[4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with optionally substituted heteroaryl or    optionally substituted heterocyclyl;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0,    1 or 2), and —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2);-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    substituted heterocyclyl, optionally substituted heterocyclylalkyl,    optionally substituted heteroaryl, optionally substituted    heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, and an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, and optionally substituted heteroarylalkyl.

Of this embodiment, a specific embodiment is a compound of formula (Ia)selected from the group consisting of:

-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[3-(piperidin-1-yl)phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(iso-propoxy)phenyl)carbonyl-3-[3-(1,3-oxazol-5-yl)phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-(4-(morpholin-4-yl)phenylamino]-1H-1,2,4-triazole;-   5-amino-3-(4-(morpholin-4-yl)phenylamino)-1-(4-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(3-(hydroxy)phenyl)carbonyl-3-(4-(morpholin-4-yl)phenylamino)-1H-1,2,4-triazole;-   5-amino-1-(4-(aminosulfonyl)phenyl)carbonyl-3-(4-(morpholin-4-yl)phenylamino)-1H-1,2,4-triazole;-   5-amino-1-(3-(methoxy)phenyl)carbonyl-3-(4-(morpholin-4-yl)phenylamino)-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-(piperidin-1-yl)phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[3-(1,3-oxazol-5-yl)phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-(tert-butoxy)phenyl)carbonyl-3-[4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole;    and-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with optionally substituted heteroaryl or    optionally substituted heterocyclyl;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of alkyl, halo, haloalkyl, nitro, cycloalkyl,    cycloalkylalkyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0,    1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,    —R⁸—N(R⁶)C(O)R¹⁰, and —R⁸—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    substituted heterocyclyl, optionally substituted heterocyclylalkyl,    optionally substituted heteroaryl, optionally substituted    heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁸—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, and an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, and optionally substituted heteroarylalkyl.

Of this embodiment, a specific embodiment is a compound of formula (Ia)selected from the group consisting of:

-   5-amino-3-(4-(morpholin-4-yl)phenylamino)-1-(3-(nitro)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole;    and-   5-amino-1-(3-(dimethylamino)phenyl)carbonyl-3-[4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with —R⁸—O—R⁹—CN, —R⁸—O—R⁹—C(O)OR¹⁰,    —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶ (where p is 0, 1 or 2),    —R⁸—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and —R⁸—N(R⁶)C(O)R¹⁰;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of alkyl, halo, haloalkyl, nitro, cycloalkyl,    cycloalkylalkyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0,    1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,    —R⁸—N(R⁶)C(O)R¹⁰, and —R⁸—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    substituted heterocyclyl, optionally substituted heterocyclylalkyl,    optionally substituted heteroaryl, optionally substituted    heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, and an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, and optionally substituted heteroarylalkyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with —R⁸—O—R⁹—CN, —R⁸—O—R⁹—C(O)OR¹⁰,    —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶ (where p is 0, 1 or 2),    —R⁸—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and —R⁸—N(R⁶)C(O)R¹⁰;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of nitro, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0,    1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,    —R⁸—N(R⁶)C(O)R¹⁰, and —R^(B)—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    substituted heterocyclyl, optionally substituted heterocyclylalkyl,    optionally substituted heteroaryl, optionally substituted    heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, and an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, and optionally substituted heteroarylalkyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Of this embodiment, a specific embodiment is a compound of formula (Ia)selected from the group consisting of:

-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[3-(methoxycarbonylmethoxy)phenylamino]-1H-1,2,4-triazole;-   5-amino-3-[4-(cyanomethoxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(cyanomethoxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-(methoxycarbonylmethoxy)phenylamino]-1H-1,2,4-triazole;-   5-amino-3-[4-[2-(dimethylamino)ethoxy]phenylamino]-1-(4-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-[2-(dimethylamino)propoxy]phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-[2-(dimethylamino)ethoxy]phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-[2-(dimethylamino)ethoxy]phenylamino]-1-(4-(dimethylamino)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[4-[2-(dimethylamino)propoxy]phenylamino]-1H-1,2,4-triazole;    and-   5-amino-3-[4-[2-(dimethylamino)propoxy]phenylamino]-1-(4-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with —R⁸—O—R⁹—CN, —R⁸—O—R⁹—C(O)OR¹⁰,    —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶ (where p is 0, 1 or 2),    —R⁸—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and —R⁸—N(R⁶)C(O)R¹⁰;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of alkyl, halo, haloalkyl, cycloalkyl, and    cycloalkylalkyl;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    substituted heterocyclyl, optionally substituted heterocyclylalkyl,    optionally substituted heteroaryl, optionally substituted    heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, and an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, and optionally substituted heteroarylalkyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Of this embodiment, a specific embodiment is a compound of formula (Ia)selected from the group consisting of:

-   5-amino-3-[3-(cyanomethoxy)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(cyanomethoxy)phenylamino]-1-(2-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(cyanomethoxy)phenylamino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(methylaminocarbonylmethoxy)phenylamino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(methoxycarbonylmethoxy)phenylamino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(N-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl)aminocarbonylmethoxy)phenylamino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-(N-(2,3-dihydroxypropyl)amino)carbonylmethoxy]-phenylamino-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-[cyclohexylaminocarbonylmethoxy]phenylamino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(3-methylphenyl)carbonyl-3-[(3-tert-butoxycarbonylmethoxy)phenyl]amino-1H-1,2,4-triazole;-   5-amino-1-(3-methylphenyl)carbonyl-3-[3-[2-(tetrahydropyran-2-yl)ethoxyaminocarbonyl]methoxy]phenylamino-1H-1,2,4-triazole;-   5-amino-3-(3-hydroxycarbonylmethoxy)phenylamino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[3-((2-hydroxyethyl)aminocarbonylmethoxy)phenyl]amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(3-methylphenyl)carbonyl-3-[3-[2-(4-morpholinyl)ethylaminocarbonylmethoxy]phenyl]amino-1H-1,2,4-triazole;-   5-amino-1-(3-methylphenyl)carbonyl-3-[3-(N-tert-butoxycarbonyl)piperazin-4-ylcarbonylmethoxy)phenyl]amino-1H-1,2,4-triazole;-   5-amino-1-(3-methylphenyl)carbonyl-3-[3-(piperazin-4-ylcarbonylmethoxy)phenyl]amino-1H-1,2,4-triazole;-   5-amino-1-(3-methylphenyl)carbonyl-3-[3-(methylsulfonylmethoxy)phenyl]amino-1H-1,2,4-triazole;-   5-amino-3-[4-[2-(dimethylamino)ethoxy]phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;    and-   5-amino-3-[4-[3-(dimethylamino)propoxy]phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is aryl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    R⁸—OR¹⁰, —R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—CN,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶ (where    p is 0, 1 or 2), —R⁸—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and    —R⁸—N(R⁶)C(O)R¹⁰;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, oxo, and    —R⁸—OR¹⁰;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁹—OR¹⁰, —R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰,    —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶ (where p is 0, 1 or 2),    —R³—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and —R⁸—N(R⁶)C(O)R¹⁰;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, oxo, and    —R⁸—OR¹⁰;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain or an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, or optionally substituted heteroarylalkyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with —R⁸—OR¹⁰ and optionally substituted    with halo or alkoxy, where R⁸ is a direct bond and R¹⁰ is selected    from the group consisting of 2-(pyrrolidin-1-yl)ethyl,    2-(piperidin-1-yl)ethyl, 2-(morpholin-4-yl)ethyl,    2-(1,3-dioxolan-2-yl)ethyl, 2-(thiomorpholin-4-yl)ethyl,    3-(pyrrolidin-1-yl)propyl, 2-(azepan-1-yl)ethyl,    2-(isoindolin-1-yl)ethyl, 2-(imidazol-1-yl)ethyl,    2-(pyrrolidin-2-on-1-yl)ethyl, and 2-(3-fluoropyrrolidin-1-yl)ethyl;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, oxo, and    —R⁸—OR¹⁰;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain or an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, or optionally substituted heteroarylalkyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Of this embodiment, a specific embodiment is a compound of formula (Ia)selected from the group consisting of:

-   5-amino-1-(3-(iso-propoxy)pyridin-5-yl)carbonyl-3-[4-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(1,3-benzodioxol-5-yl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(1,3-benzodioxol-5-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(1,4-benzodioxan-6-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(1H-indol-5-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(1H-indol-2-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(benzimidazol-6-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(6-(methyl)pyridin-3-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(pyridin-2-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(pyridin-4-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(benzo[d]thiazol-6-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(2,3-dihydrobenzofuran-5-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(1H-benzo[d][1,2,3]triazol-5-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(3-methylthien-2-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(5-methylthien-2-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(thien-2-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(quinolin-6-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(1H-indol-6-yl)carbonyl-3-[3-fluoro-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(1,2,3-thiadiazol-4-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(1H-indol-6-yl)carbonyl-3-[3-methoxy-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-(azepan-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-(isoindolin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(1H-indol-3-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(benzo[b]thiophen-2-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(benzo[b]thiophen-5-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(benzo[b]thiophen-5-yl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(benzo[b]thiophen-2-yl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   5-amino-1-(1,4-benzodioxan-6-yl)carbonyl-3-[4-[2-((S)-3-fluoropyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;    and-   5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-((S)-3-fluoropyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰,    —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶ (where p is 0, 1 or 2),    —R⁸—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, —R⁸—N(R⁶)C(O)R¹⁰, and    —R⁸—OR¹⁰ (where R¹⁰ for —R⁸—OR¹⁰ is hydrogen, alkyl, haloalkyl,    optionally substituted aryl, optionally substituted aralkyl,    optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted heterocyclyl, or optionally    substituted heteroaryl);-   R², R⁴ and R⁵ are each hydrogen;-   R³ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, oxo, and    —R⁸—OR¹⁰;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain or an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, or optionally substituted heteroarylalkyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Of this embodiment, a specific embodiment is a compound of formula (Ia)selected from the group consisting of:

-   5-amino-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-3-(4-(iso-propoxy)phenyl)amino-1H-1,2,4-triazole;-   5-amino-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-3-(4-(morpholin-4-yl)phenylamino)-1H-1,2,4-triazole;-   5-amino-3-[4-[2-(dimethylamino)ethoxy]phenylamino]-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[4-[2-(dimethylamino)propoxy]phenylamino]-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-1H-1,2,4-triazole;    and-   5-amino-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-3-[4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, halo, oxo,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁶)R⁷;-   or R¹ is heterocyclyl optionally substituted with one or more    substituents selected from the group consisting of halo, haloalkyl,    alkyl, oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷, —R⁹—S(O)_(p)R¹⁰    (where p is 0, 1 or 2) and —R⁸—N(R⁶)R⁷;-   or R¹ is heterocyclylalkyl optionally substituted with one or more    substitutents selected from the group consisting of halo, haloalkyl,    alkyl, optionally substituted aryl, optionally substituted aralkyl,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁶)R⁷;-   R² is hydrogen, alkyl or —C(O)R¹⁰;-   R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is one of the following:    -   a) alkyl optionally substituted with one or more substituents        selected from the group consisting of halo, cyano, nitro, oxo,        thioxo, trimethylsilanyl, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,        —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,        —N(R¹⁴)S(O)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t is 1        or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and —S(O)_(t)N(R¹⁴)₂        (where t is 1 or 2) where each R¹⁴ is independently hydrogen,        alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl (optionally        substituted with one or more halo groups), aralkyl,        heterocyclyl, heterocylylalkyl, heteroaryl or heteroarylalkyl;    -   b) cycloalkyl optionally substituted with one or more        substituents selected from the group consisting of —R⁸—OR¹⁰,        alkyl, halo, haloalkyl, aryl, and aralkyl;    -   c) aryl substituted with one or more substituents selected from        the group consisting of alkyl, halo, haloalkyl, nitro,        cycloalkyl, cycloalkylalkyl, optionally substituted aryl,        optionally substituted heteroaryl, optionally substituted        heterocyclyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,        —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁸)R⁷, —S(O)_(p)R⁸ (where p is        0, 1 or 2), —S(O)_(t)N(R⁸)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,        —R⁸—N(R⁸)C(O)R¹⁰ and —R⁸—CN;    -   d) aralkyl, wherein:        -   (1) the alkyl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of halo, cyano, nitro, oxo, thioxo,            trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,            —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,            —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where            t is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and            —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is            independently hydrogen, alkyl, haloalkyl, cycloalkyl,            cycloalkylalkyl, aryl (optionally substituted with one or            more halo groups), aralkyl, heterocyclyl, heterocylylalkyl,            heteroaryl or heteroarylalkyl; and        -   (2) the aryl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of alkyl, alkenyl, alkynyl, halo,            haloalkyl, haloalkenyl, haloalkynyl, cyano, nitro, aryl,            aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl,            cycloalkylalkenyl, cycloalkylalkynyl, heterocyclyl,            heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl,            heteroaryl, heteroarylalkyl, heteroarylalkenyl,            heteroarylalkynyl, —R¹⁵—OR¹⁴, —R¹⁵—OC(O)—R¹⁴, —R¹⁵—N(R¹⁴)₂,            —R¹⁵—C(O)R¹⁴, —R¹⁵—C(O)OR¹⁴, —R¹⁵—C(O)N(R¹⁴)₂,            —R¹⁵—O—R¹⁰—C(O)N(R¹⁴)₂, —R¹⁵—N(R¹⁴)C(O)OR¹⁴,            —R¹⁵—N(R¹⁴)C(O)R¹⁴, —R¹⁵—N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or            2), —R¹⁵—S(O)_(t)OR¹⁴ (where t is 1 or 2), —R¹⁵—S(O)_(p)R¹⁴            (where p is 0, 1 or 2), and —R¹⁵—S(O)_(t)N(R¹⁴)₂ (where t is            1 or 2), where each R¹⁴ is independently hydrogen, alkyl,            haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl,            heterocyclyl, heterocyclylalkyl, heteroaryl or            heteroarylalkyl, each R¹⁵ is independently a direct bond or            a straight or branched alkylene or alkenylene chain, and R¹⁶            is a straight or branched alkylene or alkenylene chain;    -   e) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, oxo,        and —R⁸—OR¹⁰; or    -   f) heteroarylalkenyl where the heteroaryl part of the        heteroarylakyl radical is optionally substituted with one or        more substituents selected from the group consisting of alkyl,        halo, haloalkyl, aryl and aralkyl;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁵, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁵ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, halo, oxo,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁸)R⁷;-   or R¹ is heterocyclyl optionally substituted with one or more    substituents selected from the group consisting of halo, haloalkyl,    alkyl, oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷, —R⁸—S(O)_(p)R¹⁰    (where p is 0, 1 or 2) and —R⁸—N(R⁶)R⁷;-   or R¹ is heterocyclylalkyl optionally substituted with one or more    substitutents selected from the group consisting of halo, haloalkyl,    alkyl, optionally substituted aryl, optionally substituted aralkyl,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁶)R⁷;-   R² is hydrogen, alkyl or —C(O)R¹⁰,-   R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is alkyl optionally substituted with one or more substituents    selected from the group consisting of halo, cyano, nitro, oxo,    thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,    —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,    —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t is 1    or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and —S(O)_(t)N(R¹⁴)₂    (where t is 1 or 2) where each R¹⁴ is independently hydrogen, alkyl,    haloalkyl, cycloalkyl, cycloalkylalkyl, aryl (optionally substituted    with one or more halo groups), aralkyl, heterocyclyl,    heterocylylalkyl, heteroaryl or heteroarylalkyl;-   or R³ is phenyl substituted with one or more substituents selected    from the group consisting of alkyl, halo, haloalkyl, nitro,    cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰,    —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0, 1 or 2),    —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰    and —R⁸—CN;-   or R³ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, oxo, and    —R⁸—OR¹⁰;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain or an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, or optionally substituted heteroarylalkyl.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is heterocyclyl optionally substituted with one or more    substituents selected from the group consisting of halo, haloalkyl,    alkyl, oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷, —R⁸—S(O)_(p)R¹⁰    (where p is 0, 1 or 2) and —R⁸—N(R⁶)R⁷;-   or R¹ is heterocyclylalkyl optionally substituted with one or more    substitutents selected from the group consisting of halo, haloalkyl,    alkyl, optionally substituted aryl, optionally substituted aralkyl,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁶)R⁷;-   R² is hydrogen, alkyl or —C(O)R¹⁰;-   R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of alkyl, halo, haloalkyl, optionally    substituted heterocyclyl, —R⁸—OR¹⁰, and —R⁸—N(R⁶)R⁷;-   or R³ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, oxo, and    —R⁸—OR¹⁰;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, and optionally substituted aralkyl;-   each R⁸ is independently selected from the group consisting of a    direct bond and an optionally substituted straight or branched    alkylene chain;-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, and    optionally substituted aralkyl.

Of this embodiment, a specific embodiment is a compound of formula (Ia)selected from the group consisting of:

-   5-amino-1-(2,6-difluorophenyl)carbonyl-3-(1-methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-(1-methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-(1-methylsulfonylpiperidin-4-yl)-amino-1H-1,2,4-triazole;-   5-amino-1-(4-(dimethylamino)phenyl)carbonyl-3-(1-methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole;-   5-amino-1-(1,4-benzodioxan-6-yl)carbonyl-3-(1-methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole;-   5-amino-1-(1H-indol-6-yl)carbonyl-3-(1-methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole;-   5-amino-1-(4-(morpholin-4-yl)phenyl)carbonyl-3-(1-methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole;-   5-amino-3-[N-(3-(4-(2-chloro-6-fluorophenyl)piperazin-1-yl)prop-1-yl)-N-((3-methylphenyl)carbonyl)amino]-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;    and-   5-amino-3-[3-(4-(2-chloro-6-fluorophenyl)piperazin-1-yl)prop-1-yl]amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, halo, oxo,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁶—N(R⁶)R⁷;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is alkyl optionally substituted with one or more substituents    selected from the group consisting of halo, cyano, nitro, oxo,    thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,    —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,    —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t is 1    or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and —S(O)_(t)N(R¹⁴)₂    (where t is 1 or 2) where each R¹⁴ is independently hydrogen, alkyl,    haloalkyl, cycloalkyl, cycloalkylalkyl, aryl (optionally substituted    with one or more halo groups), aralkyl, heterocyclyl,    heterocylylalkyl, heteroaryl or heteroarylalkyl;-   or R³ is phenyl substituted with one or more substituents selected    from the group consisting of alkyl, halo, haloalkyl, nitro,    cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰,    —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0, 1 or 2),    —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹³    and —R⁸—CN;-   or R³ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, oxo, and    —R⁸—OR¹⁰;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain or an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, or optionally substituted heteroarylalkyl.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, halo, oxo,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁶—N(R⁶)R⁷;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is alkyl optionally substituted with one or more substituents    selected from the group consisting of halo, cyano, nitro, oxo,    thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,    —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,    —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t is 1    or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and —S(O)_(t)N(R¹⁴)₂    (where t is 1 or 2) where each R¹⁴ is independently hydrogen, alkyl,    haloalkyl, cycloalkyl, cycloalkylalkyl, aryl (optionally substituted    with one or more halo groups), aralkyl, heterocyclyl,    heterocylylalkyl, heteroaryl or heteroarylalkyl;-   or R³ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, oxo, and    —R⁸—OR¹⁰;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, and optionally substituted aralkyl;-   each R⁸ is independently selected from the group consisting of a    direct bond and an optionally substituted straight or branched    alkylene chain;-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, and    optionally substituted aralkyl.

Of this embodiment, a specific embodiment is a compound of formula (Ia)selected from the group consisting of:

-   1-acetyl-5-amino-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;    and-   5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-((tert-butoxycarbonyl)aminochroman-6-yl]amino-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, halo, oxo,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁶)R⁷;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of alkyl, halo, haloalkyl, nitro, cycloalkyl,    cycloalkylalkyl, optionally substituted aryl, optionally substituted    heteroaryl, optionally substituted heterocyclyl, —R⁸—OR¹⁰,    —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁸)R⁷,    —S(O)_(p)R⁶ (where p is 0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1    or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁸)C(O)R¹⁰ and —R⁸—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, and optionally substituted aralkyl;-   each R⁸ is independently selected from the group consisting of a    direct bond and an optionally substituted straight or branched    alkylene chain;-   each R⁹ is an optionally substituted straight or branched alkylene    chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, and    optionally substituted aralkyl.

Of this embodiment, a specific embodiment is a compound of formula (Ia)selected from the group consisting of:

-   5-amino-3-[N-(2-(tetrahydropyran-2-yloxy)methylbenzofuran-5-yl)-amino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(2-(chloro)phenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-1-(4-(chloro)phenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(2-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(3-(methoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(2-(fluoro)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(4-(fluoro)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(3-(chloro)phenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(4-(methyloxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(2-(ethoxycarbonyl)benzofuran-5-yl)amino-1-(3-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(3-(fluoro)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(2-(methyloxy)phenyl)carbonyl-1H-1,2,4-triazole;-   1-(4-(acetoxy)phenyl)carbonyl-5-amino-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   1-(3-(acetoxy)phenyl)carbonyl-5-amino-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(3-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)-amino-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(4-(ethoxyphenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   1-(2-(acetoxy)phenyl)carbonyl-5-amino-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-1-(4-(cyclopentoxy)phenylcarbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-[4-(methoxycarbonylmethoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(3-(cyclopentoxy)phenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-1-(3-(ethoxy)phenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-3-(2-(hydroxymethyl)benzofuran-5-yl)amino-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-[3-(methoxycarbonylmethoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(4-(benzyloxy)phenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-[4-[2-(morpholin-4-yl)ethoxy]phenyl]carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-[3-[2-(morpholin-4-yl)ethoxy]phenyl]carbonyl-1H-1,2,4-triazole;-   5-amino-3-(indazol-5-yl)amino-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(3-(benzyloxy)phenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-3-(indazol-6-yl)amino-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(benzo[b][1,4]oxazin-3(4H)-on-6-yl)amino-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(4-(hydroxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(3-(hydroxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[(2H,3H-4-tert-butoxycarbonylbenzo[1,4]oxazin-6-yl)amino]-1-(3-methylphenyl)carbonyl-1,2,4-triazole;-   5-amino-1-(3-methylphenyl)carbonyl-3-[2-[N-[2-(tetrahydropyran-2-yloxy)ethyl]amino]carbonylbenzofuran-5-yl]amino-1H-1,2,4-triazole;-   5-amino-3-[2-[2-hydroxyethylaminocarbonyl]benzofuran-5-yl]amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-[3-[2-(1,3-dioxolan-2-yl)ethoxy]phenylcarbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-1-[4-[2-(1,3-dioxolan-2-yl)ethoxy]phenylcarbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-3-[(3,4-dihydrobenzo[1,4]oxazin-6-yl)amino]-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[2-(ethoxycarbonyl)benzofuran-5-yl]amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(3-methylphenyl)carbonyl-3-(pyridin-3-yl)amino-1H-1,2,4-triazole;-   5-amino-3-(2-methyl-2H-indazol-5-yl)-amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-[4-[2-(piperidin-1-yl)ethoxy]phenylcarbonyl-1H-1,2,4-triazole;-   5-amino-3-(2-((allyl(methyl)amino)methyl)benzofuran-5-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-[1-methyl-1H-indazol-5-yl]amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(2-((methylamino)methyl)benzofuran-5-yl)-amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(3-(2,2,2-trifluoroethoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(benzofuran-5-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(4-(2,2,2-trifluoroethoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(3-aminocarbonylmethoxy)phenylcarbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(4-iso-propylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(3,4-dimethylphenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(4-thiomethylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(3,5-dimethylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(4-nitrophenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-[(4-fluoro-3-methyl)phenyl]carbonyl-1H-1,2,4-triazole;-   5-amino-1-(4-aminophenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-[(4-trifluoromethyl)phenyl]carbonyl-1H-1,2,4-triazole;-   5-amino-1-(4-cyanophenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   1-[(4-acetylamino)phenyl]carbonyl-5-amino-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-1-[(4-dimethylamino)phenyl]carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-[(4-methylsulfonyl)phenyl]carbonyl-1H-1,2,4-triazole;-   5-amino-1-[(3-chloro-4-methyl)phenyl]carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   5-amino-3-(benzothiazol-6-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(3-methylphenyl)carbonyl-3-(6-quinolinyl)amino-1H-1,2,4-triazole;-   5-amino-3-(1H-indol-5-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1H-2-methyl-indazol-6-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1H-1-methyl-indazol-6-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1H-2-methyl-indol-5-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(benzothiazol-2-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(3-methyl-4-methoxy)phenylcarbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(3-methyl-4-iso-propoxy)phenylcarbonyl-1H-1,2,4-triazole;-   5-amino-3-(1,2-benzisothiazol-5-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(3-methyl-1,2-benzisothiazol-5-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(2,2-difluoro-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)amino-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-3-(2,2-difluoro-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)amino-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butyl)phenyl)carbonyl-3-[4-((tert-butoxycarbonyl)aminochroman-6-yl]amino-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-((tert-butoxycarbonyl)aminochroman-6-yl]amino-1H-1,2,4-triazole;-   5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-((tert-butoxycarbonyl)aminochroman-6-yl]amino-1H-1,2,4-triazole;

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is cycloalkyl optionally substituted with one or more    substituents selected from the group consisting of halo, haloalkyl,    alkyl, oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷, —R⁸—S(O)_(p)R¹⁰    (where p is 0, 1 or 2) and —R⁸—N(R⁶)R⁷;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is one of the following:    -   a) alkyl optionally substituted with one or more substituents        selected from the group consisting of halo, cyano, nitro, oxo,        thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,        —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,        —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t        is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and        —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is        independently hydrogen, alkyl, haloalkyl, cycloalkyl,        cycloalkylalkyl, aryl (optionally substituted with one or more        halo groups), aralkyl, heterocyclyl, heterocylylalkyl,        heteroaryl or heteroarylalkyl;    -   b) cycloalkyl optionally substituted with one or more        substituents selected from the group consisting of —R⁸—OR¹⁰,        alkyl, halo, haloalkyl, aryl, and aralkyl;    -   c) aryl substituted with one or more substituents selected from        the group consisting of alkyl, halo, haloalkyl, nitro,        cycloalkyl, cycloalkylalkyl, optionally substituted aryl,        optionally substituted heteroaryl, optionally substituted        heterocyclyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,        —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁸)R⁷, —S(O)_(p)R⁸ (where p is        0, 1 or 2), —S(O)_(t)N(R⁸)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,        —R⁸—N(R⁶)C(O)R¹⁰ and —R⁸—CN;    -   d) aralkyl, wherein:        -   (1) the alkyl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of halo, cyano, nitro, oxo, thioxo,            trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,            —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,            —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where            t is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and            —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is            independently hydrogen, alkyl, haloalkyl, cycloalkyl,            cycloalkylalkyl, aryl (optionally substituted with one or            more halo groups), aralkyl, heterocyclyl, heterocylylalkyl,            heteroaryl or heteroarylalkyl; and        -   (2) the aryl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of alkyl, alkenyl, alkynyl, halo,            haloalkyl, haloalkenyl, haloalkynyl, cyano, nitro, aryl,            aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl,            cycloalkylalkenyl, cycloalkylalkynyl, heterocyclyl,            heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl,            heteroaryl, heteroarylalkyl, heteroarylalkenyl,            heteroarylalkynyl, —R¹⁵—OC(O)—R¹⁴, —R¹⁶—N(R¹⁴)₂,            —R¹⁵—C(O)R¹⁴, —R¹⁵—C(O)OR¹⁴, —R¹⁵—C(O)N(R¹⁴)₂,            —R¹⁵—O—R¹⁶—C(O)N(R¹⁴)₂, —R¹⁵—N(R¹⁴)C(O)OR¹⁴,            —R¹⁵—N(R¹⁴)C(O)R¹⁴, —R¹⁵—N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or            2), —R¹⁵—S(O)_(t)OR¹⁴ (where t is 1 or 2), —R¹⁵—S(O)_(p)R¹⁴            (where p is 0, 1 or 2), and —R¹⁵—S(O)_(t)N(R¹⁴)₂ (where t is            1 or 2), where each R¹⁴ is independently hydrogen, alkyl,            haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl,            heterocyclyl, heterocyclylalkyl, heteroaryl or            heteroarylalkyl, each R¹⁵ is independently a direct bond or            a straight or branched alkylene or alkenylene chain, and R¹⁶            is a straight or branched alkylene or alkenylene chain;    -   e) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, oxo,        and —R⁸—OR¹⁰; or    -   f) heteroarylalkenyl where the heteroaryl part of the        heteroarylakyl radical is optionally substituted with one or        more substituents selected from the group consisting of alkyl,        halo, haloalkyl, aryl and aralkyl;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)—;-   R¹ is cycloalkyl optionally substituted with one or more    substituents selected from the group consisting of halo, haloalkyl,    alkyl, oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷, —R⁸—S(O)_(p)R¹³    (where p is 0, 1 or 2) and —R⁸—N(R⁶)R⁷; R², R⁴ and R⁵ are each    hydrogen;-   R³ is alkyl optionally substituted with one or more substituents    selected from the group consisting of halo, cyano, nitro, oxo,    thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,    —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,    —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t is 1    or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and —S(O)_(t)N(R¹⁴)₂    (where t is 1 or 2) where each R¹⁴ is independently hydrogen, alkyl,    haloalkyl, cycloalkyl, cycloalkylalkyl, aryl (optionally substituted    with one or more halo groups), aralkyl, heterocyclyl,    heterocylylalkyl, heteroaryl or heteroarylalkyl;-   or R³ is phenyl substituted with one or more substituents selected    from the group consisting of alkyl, halo, haloalkyl, nitro,    cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰,    —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0, 1 or 2),    —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰    and —R⁸—CN;-   or R³ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, oxo, and    —R⁸—OR¹⁰;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain or an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, or optionally substituted heteroarylalkyl.

Of this embodiment, a specific embodiment is a compound of formula (Ia)selected from the group consisting of:

-   5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[(5-(aminocarbonyl)bicyclo[2.2.1]hept-2-en-6-yl)amino]-1H-1,2,4-triazole;-   5-amino-1-(3-(tert-butoxy)phenyl)carbonyl-3-[(5-(aminocarbonyl)bicyclo[2.2.1]hept-2-en-6-yl)amino]-1H-1,2,4-triazole;-   5-amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[(5-(aminocarbonyl)bicyclo[2.2.1]hept-2-en-6-yl)amino]-1H-1,2,4-triazole;-   5-amino-1-(3-(dimethylamino)phenyl)carbonyl-3-[(5-(aminocarbonyl)bicyclo[2.2.1]hept-2-en-6-yl)amino]-1H-1,2,4-triazole;-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[(5-(aminocarbonyl)bicyclo[2.2.1]hept-2-en-6-yl)-amino]-1H-1,2,4-triazole;    and-   5-amino-1-(1H-indol-6-yl)carbonyl-3-[(5-(aminocarbonyl)bicyclo[2.2.1]hept-2-en-6-yl)amino]-1H-1,2,4-triazole.

Another embodiment of the various aspects of the invention set forthabove in the Summary of the Invention are compounds of formula (Ia):

-   wherein:

A is —C(O)O—, —C(O)N(R⁶)— or —C(S)N(R⁶)—;

-   R¹ is one of the following:    -   a) aryl substituted with one or more substituents selected from        the group consisting of halo, haloalkyl, alkyl, optionally        substituted heteroaryl, optionally substituted heterocyclyl,        —R⁸—OR¹⁰, —R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰,        —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁶—S(O)_(p)R⁶ (where p is 0, 1 or        2), —R⁸—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and        —R⁸—N(R⁶)C(O)R¹⁰; or    -   b) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, halo,        oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁶)R⁷;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is one of the following:    -   a) alkyl optionally substituted with one or more substituents        selected from the group consisting of halo, cyano, nitro, oxo,        thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,        —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,        —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t        is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and        —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is        independently hydrogen, alkyl, haloalkyl, cycloalkyl,        cycloalkylalkyl, aryl (optionally substituted with one or more        halo groups), aralkyl, heterocyclyl, heterocylylalkyl,        heteroaryl or heteroarylalkyl;    -   b) cycloalkyl optionally substituted with one or more        substituents selected from the group consisting of —R⁸—OR¹⁰,        alkyl, halo, haloalkyl, aryl, and aralkyl;    -   c) aryl substituted with one or more substituents selected from        the group consisting of alkyl, halo, haloalkyl, nitro,        cycloalkyl, cycloalkylalkyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰,        —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷,        —S(O)_(p)R⁶ (where p is 0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is        1 or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰ and —R⁸—CN;    -   d) aralkyl, wherein:        -   (1) the alkyl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of halo, cyano, nitro, oxo, thioxo,            trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,            —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,            —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where            t is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and            —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is            independently hydrogen, alkyl, haloalkyl, cycloalkyl,            cycloalkylalkyl, aryl (optionally substituted with one or            more halo groups), aralkyl, heterocyclyl, heterocylylalkyl,            heteroaryl or heteroarylalkyl; and        -   (2) the aryl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of alkyl, alkenyl, alkynyl, halo,            haloalkyl, haloalkenyl, haloalkynyl, cyano, nitro, aryl,            aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl,            cycloalkylalkenyl, cycloalkylalkynyl, heterocyclyl,            heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl,            heteroaryl, heteroarylalkyl, heteroarylalkenyl,            heteroarylalkynyl, —R¹⁵—OR¹⁴, —R¹⁵—OC(O)—R¹⁴, —R¹⁵—N(R¹⁴)₂,            —R¹⁵—C(O)R¹⁴, —R¹⁵—C(O)OR¹⁴, —R¹⁵—C(O)N(R¹⁴)₂,            —R¹⁵—O—R¹⁶—C(O)N(R¹⁴)₂, —R¹⁵—N(R¹⁴)C(O)OR¹⁴,            —R¹⁵—N(R¹⁴)C(O)R¹⁴, —R¹⁵—N(R¹⁴)S(O)R¹⁴ (where t is 1 or 2),            —R¹⁵—S(O)_(t)OR¹⁴ (where t is 1 or 2), —R¹⁵—S(O)_(p)R¹⁴            (where p is 0, 1 or 2), and —R¹⁵—S(O)_(t)N(R¹⁴)₂ (where t is            1 or 2), where each R¹⁴ is independently hydrogen, alkyl,            haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl,            heterocyclyl, heterocyclylalkyl, heteroaryl or            heteroarylalkyl, each R¹⁵ is independently a direct bond or            a straight or branched alkylene or alkenylene chain, and R¹⁶            is a straight or branched alkylene or alkenylene chain;    -   e) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, oxo,        and —R⁸—OR¹⁰; or    -   f) heteroarylalkenyl where the heteroaryl part of the        heteroarylakyl radical is optionally substituted with one or        more substituents selected from the group consisting of alkyl,        halo, haloalkyl, aryl and aralkyl;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—NO₂, —R⁹—N(R¹⁰)₂, —R⁹—C(O)OR¹⁰ and    —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Another embodiment of the compounds of formula (Ia) are compounds offormula (Ia) wherein:

-   A is —C(O)O—, —C(O)N(R⁶)— or —C(S)N(R⁶)—;-   R¹ is aryl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—OR¹⁰, —R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—CN,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶ (where    p is 0, 1 or 2), —R⁸—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and    —R⁸—N(R⁶)C(O)R¹⁰;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is cycloalkyl optionally substituted with one or more    substituents selected from the group consisting of —R⁸—OR¹⁰, alkyl,    halo, haloalkyl, aryl, and aralkyl;-   or R³ is phenyl substituted with one or more substituents selected    from the group consisting of alkyl, halo, haloalkyl, nitro,    cycloalkyl, cycloalkylalkyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0,    1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,    —R⁸—N(R⁶)C(O)R¹⁰, and —R⁸—CN;-   or R³ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, oxo, and    —R⁸—OR¹⁰;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    substituted heterocyclyl, optionally substituted heterocyclylalkyl,    optionally substituted heteroaryl, optionally substituted    heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain or an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain or an    optionally substituted straight or branched alkenylene chain;-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, or optionally substituted heteroarylalkyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Of this embodiment, a specific embodiment is a compound of formula (Ia)selected from the group consisting of:

-   5-amino-N-(4-chlorophenyl)-3-[4-(methoxy)phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(3,5-(dimethyl)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(4-(dimethylamino)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-3-(4-methoxyphenyl)amino-1-(tert-butoxycarbonyl)-1H-1,2,4-triazole;-   3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-(4-chlorophenyl)-1H-1,2,4-triazole-1-carboxamide;-   3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-(1,3-benzodioxol-5-yl)-1H-1,2,4-triazole-1-carboxamide;-   3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-cyclopentyl-1H-1,2,4-triazole-1-carboxamide;-   3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-(4-(iso-propyl)phenyl)-1H-1,2,4-triazole-1-carboxamide;-   3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-(4-(butoxy)phenyl)-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(4-(iso-propyl)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(4-butoxyphenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(4-methylphenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(4-(methoxy)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-cyclohexyl-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(1,3-benzodioxol-5-yl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(3-methylphenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(3-methoxyphenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(3,5-(dimethoxy)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-cyclohexyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-cyclopentyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(4-methylphenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(3-methoxyphenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(4-cyanophenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(1,3-benzodioxol-5-yl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(3-methylphenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(3,5-(dimethoxy)phenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(3,4-(dimethoxy)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-N-(3,4-(dimethyl)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   5-amino-3-[4-(piperidin-1-yl)phenylamino]-1-(tert-butoxycarbonyl)-1H-1,2,4-triazole;-   5-amino-N-(2,4,6-trifluorophenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carbothioamide;    and-   5-amino-N-(2,6-difluorophenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carbothioamide.

Another embodiment of the various aspects of the invention set forthabove in the Summary of the Invention are compounds of formula (Ib):

-   wherein:-   A is —C(O)—;-   R¹ is one of the following:    -   a) aryl substituted with one or more substituents selected from        the group consisting of halo, haloalkyl, alkyl, optionally        substituted heteroaryl, optionally substituted heterocyclyl,        —R⁸—OR¹⁰, R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—CN,        —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁸)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶        (where p is 0, 1 or 2), —R⁸—O—R⁹—N(R⁸)R⁷,        —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and —R⁸—N(R⁶)C(O)R¹⁰; or    -   b) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, halo,        oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁶)R⁷; or    -   c) heterocyclyl optionally substituted with one or more        substituents selected from the group consisting of halo,        haloalkyl, alkyl, oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷,        —R⁸—S(O)_(p)R¹⁰ (where p is 0, 1 or 2) and —R⁸—N(R⁶)R⁷;    -   d) heterocyclylalkyl optionally substituted with one or more        substitutents selected from the group consisting of halo,        haloalkyl, alkyl, optionally substituted aryl, optionally        substituted aralkyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and        —R⁸—N(R⁶)R⁷; or    -   e) cycloalkyl optionally substituted with one or more        substituents selected from the group consisting of halo,        haloalkyl, alkyl, oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷,        —R⁸—S(O)_(p)R¹⁰ (where p is 0, 1 or 2) and —R⁸—N(R⁸)R⁷;-   R² is hydrogen, alkyl or —C(O)R¹⁰;-   R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is one of the following:    -   a) alkyl optionally substituted with one or more substituents        selected from the group consisting of halo, cyano, nitro, oxo,        thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,        —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,        —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t        is 1 or 2), S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and        —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is        independently hydrogen, alkyl, haloalkyl, cycloalkyl,        cycloalkylalkyl, aryl (optionally substituted with one or more        halo groups), aralkyl, heterocyclyl, heterocylylalkyl,        heteroaryl or heteroarylalkyl;    -   b) cycloalkyl optionally substituted with one or more        substituents selected from the group consisting of —R⁸—OR¹⁰,        alkyl, halo, haloalkyl, aryl, and aralkyl;    -   c) aryl substituted with one or more substituents selected from        the group consisting of alkyl, halo, haloalkyl, nitro,        cycloalkyl, cycloalkylalkyl, optionally substituted aryl,        optionally substituted heteroaryl, optionally substituted        heterocyclyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,        —R⁸—O—R⁸—C(O)OR¹⁰, —R⁸—O—R⁸—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is        0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,        —R⁸—N(R⁶)C(O)R¹⁰ and —R⁸—CN;    -   d) aralkyl, wherein:        -   (1) the alkyl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of halo, cyano, nitro, oxo, thioxo,            trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,            —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,            —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where            t is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and            —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is            independently hydrogen, alkyl, haloalkyl, cycloalkyl,            cycloalkylalkyl, aryl (optionally substituted with one or            more halo groups), aralkyl, heterocyclyl, heterocylylalkyl,            heteroaryl or heteroarylalkyl; and        -   (2) the aryl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of alkyl, alkenyl, alkynyl, halo,            haloalkyl, haloalkenyl, haloalkynyl, cyano, nitro, aryl,            aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl,            cycloalkylalkenyl, cycloalkylalkynyl, heterocyclyl,            heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl,            heteroaryl, heteroarylalkyl, heteroarylalkenyl,            heteroarylalkynyl, —R¹⁵—OR¹⁴, —R¹⁵—OC(O)—R¹⁴, —R¹⁵—N(R¹⁴)₂,            —R¹⁵—C(O)R¹⁴, —R¹⁵—C(O)OR¹⁴, —R¹⁵—C(O)N(R¹⁴)₂,            —R¹⁵—O—R¹⁶—C(O)N(R¹⁴)₂, —R¹⁵—N(R¹⁴)C(O)OR¹⁴,            —R¹⁵—N(R¹⁴)C(O)R¹⁴, —R¹⁵—N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or            2), —R¹⁵—S(O)_(t)OR¹⁴ (where t is 1 or 2), —R¹⁵—S(O)_(p)R¹⁴            (where p is 0, 1 or 2), and —R¹⁵—S(O)_(t)N(R¹⁴)₂ (where t is            1 or 2), where each R¹⁴ is independently hydrogen, alkyl,            haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl,            heterocyclyl, heterocyclylalkyl, heteroaryl or            heteroarylalkyl, each R¹⁵ is independently a direct bond or            a straight or branched alkylene or alkenylene chain, and R¹⁶            is a straight or branched alkylene or alkenylene chain;    -   e) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, oxo,        and —R⁸—OR¹⁰; or    -   f) heteroarylalkenyl where the heteroaryl part of the        heteroarylakyl radical is optionally substituted with one or        more substituents selected from the group consisting of alkyl,        halo, haloalkyl, aryl and aralkyl;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Another embodiment of the compounds of formula (Ib) are compounds offormula (Ib) wherein:

-   A is —C(O)—;-   R¹ is one of the following:    -   a) aryl substituted with one or more substituents selected from        the group consisting of halo, haloalkyl, alkyl, optionally        substituted heteroaryl, optionally substituted heterocyclyl,        —R⁸—OR¹⁰, —R⁸—O—R⁸—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—CN,        —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶        (where p is 0, 1 or 2), —R⁸—O—R⁹—N(R⁶)R⁷,        —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and —R⁸—N(R⁶)C(O)R¹⁰; or    -   b) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, halo,        oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁶)R⁷; or    -   c) heterocyclyl optionally substituted with one or more        substituents selected from the group consisting of halo,        haloalkyl, alkyl, oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷,        —R⁸—S(O)_(p)R¹⁰ (where p is 0, 1 or 2) and —R⁸—N(R⁶)R⁷;    -   d) heterocyclylalkyl optionally substituted with one or more        substitutents selected from the group consisting of halo,        haloalkyl, alkyl, optionally substituted aryl, optionally        substituted aralkyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and        —R⁸—N(R⁶)R⁷; or    -   e) cycloalkyl optionally substituted with one or more        substituents selected from the group consisting of halo,        haloalkyl, alkyl, oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷,        —R⁸—S(O)_(p)R¹⁰ (where p is 0, 1 or 2) and —R⁸—N(R⁶)R⁷;-   R² is hydrogen, alkyl or —C(O)R¹⁰;-   R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is one of the following:    -   a) alkyl optionally substituted with one or more substituents        selected from the group consisting of halo, cyano, nitro, oxo,        thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,        —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,        —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t        is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and        —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is        independently hydrogen, alkyl, haloalkyl, cycloalkyl,        cycloalkylalkyl, aryl (optionally substituted with one or more        halo groups), aralkyl, heterocyclyl, heterocylylalkyl,        heteroaryl or heteroarylalkyl;    -   b) cycloalkyl optionally substituted with one or more        substituents selected from the group consisting of —R⁸—OR¹⁰,        alkyl, halo, haloalkyl, aryl, and aralkyl;    -   c) aryl substituted with one or more substituents selected from        the group consisting of alkyl, halo, haloalkyl, nitro,        cycloalkyl, cycloalkylalkyl, optionally substituted aryl,        optionally substituted heteroaryl, optionally substituted        heterocyclyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,        —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is        0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,        —R⁸—N(R⁶)C(O)R¹⁰ and —R⁸—CN;    -   d) aralkyl, wherein:        -   (1) the alkyl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of halo, cyano, nitro, oxo, thioxo,            trimethylsilanyl, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴, —C(O)OR¹⁴,            —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,            —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where            t is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and            —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is            independently hydrogen, alkyl, haloalkyl, cycloalkyl,            cycloalkylalkyl, aryl (optionally substituted with one or            more halo groups), aralkyl, heterocyclyl, heterocylylalkyl,            heteroaryl or heteroarylalkyl; and        -   (2) the aryl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of alkyl, alkenyl, alkynyl, halo,            haloalkyl, haloalkenyl, haloalkynyl, cyano, nitro, aryl,            aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl,            cycloalkylalkenyl, cycloalkylalkynyl, heterocyclyl,            heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl,            heteroaryl, heteroarylalkyl, heteroarylalkenyl,            heteroarylalkynyl, —R¹⁵—OR¹⁴, —R¹⁵—OC(O)—R¹⁴, —R¹⁵—N(R¹⁴)₂,            —R¹⁵—C(O)R¹⁴, —R¹⁵—C(O)OR¹⁴, —R¹⁵—C(O)N(R¹⁴)₂,            —R¹⁵—O—R¹⁶—C(O)N(R¹⁴)₂, —R¹⁵—N(R¹⁴)C(O)OR¹⁴,            —R¹⁵—N(R¹⁴)C(O)R¹⁴, —R¹⁵—N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or            2), —R¹⁵—S(O)_(t)OR¹⁴ (where t is 1 or 2), —R¹⁵—S(O)_(p)R¹⁴            (where p is 0, 1 or 2), and —R¹⁵—S(O)_(t)N(R¹⁴)₂ (where t is            1 or 2), where each R¹⁴ is independently hydrogen, alkyl,            haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl,            heterocyclyl, heterocyclylalkyl, heteroaryl or            heteroarylalkyl, each R¹⁵ is independently a direct bond or            a straight or branched alkylene or alkenylene chain, and R¹⁶            is a straight or branched alkylene or alkenylene chain;    -   e) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, oxo,        and —R⁸—OR¹⁰; or    -   f) heteroarylalkenyl where the heteroaryl part of the        heteroarylakyl radical is optionally substituted with one or        more substituents selected from the group consisting of alkyl,        halo, haloalkyl, aryl and aralkyl;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Another embodiment of the compounds of formula (Ib) are compounds offormula (Ib) wherein:

-   A is —C(O)—;-   R¹ is aryl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—OR¹⁰, —R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰,    —R⁸—O—R⁹—C(O)N(R⁸)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶ (where p is 0, 1 or 2),    —R⁸—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and —R⁸—N(R⁶)C(O)R¹⁰;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is one of the following:    -   a) alkyl optionally substituted with one or more substituents        selected from the group consisting of halo, cyano, nitro, oxo,        thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,        —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,        —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t        is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and        —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is        independently hydrogen, alkyl, haloalkyl, cycloalkyl,        cycloalkylalkyl, aryl (optionally substituted with one or more        halo groups), aralkyl, heterocyclyl, heterocylylalkyl,        heteroaryl or heteroarylalkyl;    -   b) cycloalkyl optionally substituted with one or more        substituents selected from the group consisting of —R⁸—OR¹⁰,        alkyl, halo, haloalkyl, aryl, and aralkyl;    -   c) aryl substituted with one or more substituents selected from        the group consisting of alkyl, halo, haloalkyl, nitro,        cycloalkyl, cycloalkylalkyl, optionally substituted aryl,        optionally substituted heteroaryl, optionally substituted        heterocyclyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,        —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is        0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,        —R⁸—N(R⁶)C(O)R¹⁰ and —R⁸—CN;    -   d) aralkyl, wherein:        -   (1) the alkyl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of halo, cyano, nitro, oxo, thioxo,            trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,            —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,            —N(R¹⁴)S(O)_(t)R¹⁴, (where t is 1 or 2), —S(O)_(t)OR¹⁴            (where t is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2),            and —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is            independently hydrogen, alkyl, haloalkyl, cycloalkyl,            cycloalkylalkyl, aryl (optionally substituted with one or            more halo groups), aralkyl, heterocyclyl, heterocylylalkyl,            heteroaryl or heteroarylalkyl; and        -   (2) the aryl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of alkyl, alkenyl, alkynyl, halo,            haloalkyl, haloalkenyl, haloalkynyl, cyano, nitro, aryl,            aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl,            cycloalkylalkenyl, cycloalkylalkynyl, heterocyclyl,            heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl,            heteroaryl, heteroarylalkyl, heteroarylalkenyl,            heteroarylalkynyl, —R¹⁵—OR¹⁴, —R¹⁵—OC(O)—R¹⁴, —R¹⁵—N(R¹⁴)₂,            —R¹⁵—C(O)R¹⁴, —R¹⁵—C(O)OR¹⁴, —R¹⁵—C(O)N(R¹⁴)₂,            —R¹⁵—O—R¹⁶—C(O)N(R¹⁴)₂, —R¹⁵—N(R¹⁴)C(O)OR¹⁴,            —R¹⁵—N(R¹⁴)C(O)R¹⁴, —R¹⁵—N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or            2), —R¹⁵—S(O)_(t)OR¹⁴ (where t is 1 or 2), —R¹⁵—S(O)_(p)R¹⁴            (where p is 0, 1 or 2), and —R¹⁵—S(O)_(t)N(R¹⁴)₂ (where t is            1 or 2), where each R¹⁴ is independently hydrogen, alkyl,            haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl,            heterocyclyl, heterocyclylalkyl, heteroaryl or            heteroarylalkyl, each R¹⁵ is independently a direct bond or            a straight or branched alkylene or alkenylene chain, and R¹⁶            is a straight or branched alkylene or alkenylene chain;    -   e) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, oxo,        and —R⁸—OR¹⁰; or    -   f) heteroarylalkenyl where the heteroaryl part of the        heteroarylakyl radical is optionally substituted with one or        more substituents selected from the group consisting of alkyl,        halo, haloalkyl, aryl and aralkyl;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Another embodiment of the compounds of formula (Ib) are compounds offormula (Ib) wherein:

-   A is —C(O)—;-   R¹ is aryl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—OR¹⁰, —R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—CN,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁸)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁸ (where    p is 0, 1 or 2), —R⁸—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and    —R⁸—N(R⁶)C(O)R¹⁰;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is cycloalkyl optionally substituted with —R⁸—OR¹⁰;-   or R³ is aryl substituted with one or more substituents selected    from the group consisting of alkyl, halo, haloalkyl, nitro,    cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰,    —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0, 1 or 2),    —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰,    and —R⁸—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Another embodiment of the compounds of formula (Ib) are compounds offormula (Ib) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁶—OR¹⁰, —R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁸—OR¹⁰, —R⁸—O—R⁹—CN,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶ (where    p is 0, 1 or 2), —R⁸—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and    —R⁸—N(R⁶)C(O)R¹⁰;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is cycloalkyl optionally substituted with —R⁸—OR¹⁰; or-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of alkyl, halo, haloalkyl, nitro, cycloalkyl,    cycloalkylalkyl, optionally substituted aryl, optionally substituted    heteroaryl, optionally substituted heterocyclyl, —R⁸—OR¹⁰,    —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷,    —S(O)_(p)R⁶ (where p is 0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1    or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰, and —R⁸—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Another embodiment of the compounds of formula (Ib) are compounds offormula (Ib) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with one or two substituents selected from    the group consisting of halo, haloalkyl, alkyl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—OR¹⁰, —R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—CN,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶ (where    p is 0, 1 or 2), —R⁸—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and    —R⁸—N(R⁶)C(O)R¹⁰;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is cycloalkyl optionally substituted with —R⁸—OR¹⁰;-   or R³ is phenyl substituted with one or more substituents selected    from the group consisting of alkyl, halo, haloalkyl, nitro,    cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰,    —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0, 1 or 2),    —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰,    and —R⁸—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    substituted heterocyclyl, optionally substituted heterocyclylalkyl,    optionally substituted heteroaryl, optionally substituted    heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, and an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, and optionally substituted heteroarylalkyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Another embodiment of the compounds of formula (Ib) are compounds offormula (Ib) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, —R⁸—OR¹⁰,    —R⁸—O—R⁹—OR¹⁰, and —R⁸—O—R⁹—O—R⁹—OR¹⁰;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is cycloalkyl optionally substituted with —R⁸—OR¹⁰;-   or R³ is phenyl substituted with one or more substituents selected    from the group consisting of alkyl, halo, haloalkyl, nitro,    cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰,    —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0, 1 or 2),    —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰,    and —R⁸—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    substituted heterocyclyl, optionally substituted heterocyclylalkyl,    optionally, substituted heteroaryl, optionally substituted    heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, and an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, and optionally substituted heteroarylalkyl.

Of this embodiment, a specific embodiment is a compound of formula (Ib)selected from the group consisting of:

-   3-amino-1-(4-(iso-propoxy)phenyl)carbonyl-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   3-amino-5-[4-(iso-propoxy)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   3-amino-1-(4-iso-propoxyphenyl)carbonyl-5-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   3-amino-1-(4-(tert-butyl)phenyl)carbonyl-5-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;    and-   3-amino-1-(4-(morpholin-4-yl)phenyl)carbonyl-5-[3-fluoro-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ib) are compounds offormula (Ib) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with optionally substituted heteroaryl or    optionally substituted heterocyclyl;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of alkyl, halo, haloalkyl, nitro, cycloalkyl,    cycloalkylalkyl, optionally substituted aryl, optionally substituted    heteroaryl, optionally substituted heterocyclyl, —R⁸—OR¹⁰,    —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷,    —S(O)_(p)R⁶ (where p is 0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1    or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰, and —R⁸—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    substituted heterocyclyl, optionally substituted heterocyclylalkyl,    optionally substituted heteroaryl, optionally substituted    heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, and an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, and optionally substituted heteroarylalkyl.

Of this embodiment, a specific embodiment is a compound of formula (Ib)selected from the group consisting of:

-   3-amino-1-(4-(iso-propoxy)phenyl)carbonyl-5-(4-(morpholin-4-yl)phenylamino]-1H-1,2,4-triazole;-   3-amino-5-(4-(morpholin-4-yl)phenylamino)-1-(4-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole;-   3-amino-1-(3-(chloro)phenyl)carbonyl-5-(4-(morpholin-4-yl)phenylamino)-1H-1,2,4-triazole;-   3-amino-1-(4-(iso-propoxy)phenyl)carbonyl-5-[4-(piperidin-1-yl)phenylamino]-1H-1,2,4-triazole;-   3-amino-1-(4-(tert-butoxy)phenyl)carbonyl-5-(4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole;-   3-amino-1-(4-(iso-propoxy)phenyl)carbonyl-5-(4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole;-   3-amino-1-(4-(tert-butyl)phenyl)carbonyl-5-[4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole;-   3-amino-1-(4-methylphenyl)carbonyl-5-(4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole;-   3-amino-1-(4-(iso-propoxy)phenyl)carbonyl-5-(4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole;-   3-amino-1-(4-(dimethylamino)phenyl)carbonyl-5-(4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole;    and-   3-amino-1-(3-(dimethylamino)phenyl)carbonyl-5-(4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ib) are compounds offormula (Ib) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with —R⁸—O—R⁹—CN, —R⁸—O—R⁹—C(O)OR¹⁰,    —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶ (where p is 0, 1 or 2),    —R⁸—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and —R⁸—N(R⁶)C(O)R¹⁰;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is phenyl substituted with one or more substituents selected from    the group consisting of alkyl, halo, haloalkyl, nitro, cycloalkyl,    cycloalkylalkyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0,    1 or 2), —S(O)_(t)N(R⁸)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,    —R⁸—N(R⁶)C(O)R¹⁰, and —R⁸—CN;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    substituted heterocyclyl, optionally substituted heterocyclylalkyl,    optionally substituted heteroaryl, optionally substituted    heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, and an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, and optionally substituted heteroarylalkyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Of this embodiment, a specific embodiment is the following compound offormula (Ib), i.e.,3-amino-5-[3-[cyclohexylaminocarbonylmethoxy]phenylamino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ib) are compounds offormula (Ib) wherein:

-   A is —C(O)—;-   R¹ is aryl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—OR¹⁰, —R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—CN,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶ (where    p is 0, 1 or 2), —R⁸—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and    —R⁸—N(R⁶)C(O)R¹⁰;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, oxo, and    —R⁸—OR¹⁰;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Another embodiment of the compounds of formula (Ib) are compounds offormula (Ib) wherein:

-   A is —C(O)—;-   R¹ is phenyl substituted with one or more substituents selected from    the group consisting of halo, haloalkyl, alkyl, optionally    substituted heteroaryl, optionally substituted heterocyclyl,    —R⁸—OR¹⁰, —R⁸—O—R⁹—OR¹⁰, —R⁶—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—CN,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶ (where    p is 0, 1 or 2), —R⁸—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and    —R⁸—N(R⁶)C(O)R¹⁰;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, oxo, and    —R⁸—OR¹⁰;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain or an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, or optionally substituted heteroarylalkyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Of this embodiment, a specific embodiment is a compound of formula (Ib)selected from the group consisting of:

-   3-amino-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-5-(4-(iso-propoxy)phenyl)amino-1H-1,2,4-triazole;-   3-amino-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-5-(4-(morpholin-4-yl)phenylamino)-1H-1,2,4-triazole;-   3-amino-1-(1H-indol-5-yl)carbonyl-5-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   3-amino-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-5-[4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole;-   3-amino-1-(benzo[b]thiophen-2-yl)carbonyl-5-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   3-amino-1-(1H-indol-6-yl)carbonyl-5-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   3-amino-1-(benzo[b]thiophen-5-yl)carbonyl-5-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;-   3-amino-1-(1,4-benzodioxan-6-yl)carbonyl-5-[4-[2-((S)-3-fluoropyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole;    and-   3-amino-1-(1H-indol-6-yl)carbonyl-5-[4-[2-((S)-3-fluoropyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ib) are compounds offormula (Ib) wherein:

-   A is —C(O)—;-   R¹ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, halo, oxo,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁶)R⁷;-   or R¹ is heterocyclylalkyl optionally substituted with one or more    substitutents selected from the group consisting of halo, haloalkyl,    alkyl, optionally substituted aryl, optionally substituted aralkyl,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁶)R⁷;-   or R¹ is cycloalkyl optionally substituted with one or more    substituents selected from the group consisting of halo, haloalkyl,    alkyl, oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷, —R⁸—S(O)_(p)R¹⁰    (where p is 0, 1 or 2) and —R⁸—N(R⁶)R⁷;-   R² is hydrogen, alkyl or —C(O)R¹⁰;-   R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is one of the following:    -   a) alkyl optionally substituted with one or more substituents        selected from the group consisting of halo, cyano, nitro, oxo,        thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,        —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,        —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t        is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and        —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is        independently hydrogen, alkyl, haloalkyl, cycloalkyl,        cycloalkylalkyl, aryl (optionally substituted with one or more        halo groups), aralkyl, heterocyclyl, heterocylylalkyl,        heteroaryl or heteroarylalkyl;    -   b) cycloalkyl optionally substituted with one or more        substituents selected from the group consisting of —R⁸—OR¹⁰,        alkyl, halo, haloalkyl, aryl, and aralkyl;    -   c) aryl substituted with one or more substituents selected from        the group consisting of alkyl, halo, haloalkyl, nitro,        cycloalkyl, cycloalkylalkyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰,        —R⁸—OC(O)R¹⁰, —R⁸—O—R⁸—C(O)OR¹⁰, —R⁸—O—R⁸—C(O)N(R⁶)R⁷,        —S(O)_(p)R⁶ (where p is 0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is        1 or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰ and —R⁸—CN;    -   d) aralkyl, wherein:        -   (1) the alkyl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of halo, cyano, nitro, oxo, thioxo,            trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,            —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,            —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where            t is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and            —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is            independently hydrogen, alkyl, haloalkyl, cycloalkyl,            cycloalkylalkyl, aryl (optionally substituted with one or            more halo groups), aralkyl, heterocyclyl, heterocylylalkyl,            heteroaryl or heteroarylalkyl; and    -   (2) the aryl part of the aralkyl radical is optionally        substituted with one or more substituents selected from the        group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl,        haloalkenyl, haloalkynyl, cyano, nitro, aryl, aralkyl,        aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl,        cycloalkylalkenyl, cycloalkylalkynyl, heterocyclyl,        heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl,        heteroaryl, heteroarylalkyl, heteroarylalkenyl,        heteroarylalkynyl, —R¹⁵—OR¹⁴, —R¹⁵—OC(O)—R¹⁴, —R¹⁵—N(R¹⁴)₂,        —R¹⁵—C(O)R¹⁴, —R¹⁵—C(O)OR¹⁴, —R¹⁵—C(O)N(R¹⁴)₂,        —R¹⁵—O—R¹⁶—C(O)N(R¹⁴)₂, —R¹⁵—N(R¹⁴)C(O)OR¹⁴, —R¹⁵—N(R¹⁴)C(O)R¹⁴,        —R¹⁵—N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —R¹⁵—S(O)_(t)OR¹⁴        (where t is 1 or 2), —R¹⁵—S(O)_(p)R¹⁴ (where p is 0, 1 or 2),        and —R¹⁵—S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2), where each R¹⁴ is        independently hydrogen, alkyl, haloalkyl, cycloalkyl,        cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl,        heteroaryl or heteroarylalkyl, each R¹⁵ is independently a        direct bond or a straight or branched alkylene or alkenylene        chain, and R¹⁶ is a straight or branched alkylene or alkenylene        chain;    -   e) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, oxo,        and —R⁸—OR¹⁰; or    -   f) heteroarylalkenyl where the heteroaryl part of the        heteroarylakyl radical is optionally substituted with one or        more substituents selected from the group consisting of alkyl,        halo, haloalkyl, aryl and aralkyl;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl.

Another embodiment of the compounds of formula (Ib) are compounds offormula (Ib) wherein:

-   A is —C(O)—;-   R¹ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, halo, oxo,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁶)R⁷;-   or R¹ is heterocyclylalkyl optionally substituted with one or more    substitutents selected from the group consisting of halo, haloalkyl,    alkyl, optionally substituted aryl, optionally substituted aralkyl,    —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁶)R⁷;-   or R¹ is cycloalkyl optionally substituted with one or more    substituents selected from the group consisting of halo, haloalkyl,    alkyl, oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷, —R⁸—S(O)_(p)R¹⁰    (where p is 0, 1 or 2) and —R⁸—N(R⁶)R⁷;-   R² is hydrogen, alkyl or —C(O)R¹⁰;-   R⁴ and R⁵ are each hydrogen or alkyl;-   R³ is alkyl optionally substituted with one or more substituents    selected from the group consisting of halo, cyano, nitro, oxo,    thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,    —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,    —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t is 1    or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and —S(O)_(t)N(R¹⁴)₂    (where t is 1 or 2) where each R¹⁴ is independently hydrogen, alkyl,    haloalkyl, cycloalkyl, cycloalkylalkyl, aryl (optionally substituted    with one or more halo groups), aralkyl, heterocyclyl,    heterocylylalkyl, heteroaryl or heteroarylalkyl;-   or R³ is phenyl substituted with one or more substituents selected    from the group consisting of alkyl, halo, haloalkyl, nitro,    cycloalkyl, cycloalkylalkyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁵,    —R⁸—O—R³—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0,    1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,    —R⁸—N(R⁶)C(O)R¹⁰ and —R⁸—CN;-   or R³ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, oxo, and    —R⁸—OR¹⁰;-   each R⁶ and R⁷ is independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain or an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, or optionally substituted heteroarylalkyl.

Of this embodiment, a specific embodiment is a compound of formula (Ib)selected from the group consisting of:

-   3-amino-5-[(2H,3H-4-tert-butoxycarbonylbenzo[1,4]oxazin-6-yl)-[(2H,3H-4-tert-butoxycarbonylbenzo[1,4]oxazin-6-yl)amino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole;-   3-amino-1-[3-[2-(1,3-dioxolan-2-yl)ethoxy]phenylcarbonyl-5-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   3-amino-1-[4-[2-(1,3-dioxolan-2-yl)ethoxy]phenylcarbonyl-5-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   3-amino-5-(1,4-benzodioxan-6-yl)amino-1-(4-iso-propylphenyl)carbonyl-1H-1,2,4-triazole;-   3-amino-1-(3,4-dimethylphenyl)carbonyl-5-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   3-amino-1-(3-(benzyloxy)phenyl)carbonyl-5-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole;-   3-amino-5-(1,4-benzodioxan-6-yl)amino-1-(4-thiomethylphenyl)carbonyl-1H-1,2,4-triazole;-   3-amino-5-(1,4-benzodioxan-6-yl)amino-1-[(4-fluoro-3-methyl)phenyl]carbonyl-1H-1,2,4-triazole-   3-amino-1-(2,6-difluorophenyl)carbonyl-5-(1-methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole;-   3-amino-1-(4-(dimethylamino)phenyl)carbonyl-5-(1-methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole;    and-   3-amino-5-[3-(4-(2-chloro-6-fluorophenyl)piperazin-1-yl)prop-1-yl]amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole.

Another embodiment of the compounds of formula (Ib) are compounds offormula (Ib) wherein:

-   A is —C(O)—;-   R¹ is cycloalkyl optionally substituted with one or more    substituents selected from the group consisting of halo, haloalkyl,    alkyl, oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷, —R⁸—S(O)_(p)R¹⁰    (where p is 0, 1 or 2) and —R⁸—N(R⁶)R⁷;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is one of the following:    -   a) alkyl optionally substituted with one or more substituents        selected from the group consisting of halo, cyano, nitro, oxo,        thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂,        —C(O)R¹⁴—C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,        —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t        is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and        —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is        independently hydrogen, alkyl, haloalkyl, cycloalkyl,        cycloalkylalkyl, aryl (optionally substituted with one or more        halo groups), aralkyl, heterocyclyl, heterocylylalkyl,        heteroaryl or heteroarylalkyl;    -   b) cycloalkyl optionally substituted with one or more        substituents selected from the group consisting of —R⁸—OR¹⁰,        alkyl, halo, haloalkyl, aryl, and aralkyl;    -   c) aryl substituted with one or more substituents selected from        the group consisting of alkyl, halo, haloalkyl, nitro,        cycloalkyl, cycloalkylalkyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰,        —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁸—C(O)N(R⁸)R⁷,        —S(O)_(p)R⁸ (where p is 0, 1 or 2), —S(O)_(t)N(R⁸)R⁷ (where t is        1 or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁸)C(O)R¹⁰ and —R⁸—CN;    -   d) aralkyl, wherein:        -   (1) the alkyl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of halo, cyano, nitro, oxo, thioxo,            trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)², —C(O)R¹⁴,            —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,            —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where            t is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and            —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is            independently hydrogen, alkyl, haloalkyl, cycloalkyl,            cycloalkylalkyl, aryl (optionally substituted with one or            more halo groups), aralkyl, heterocyclyl, heterocylylalkyl,            heteroaryl or heteroarylalkyl; and        -   (2) the aryl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of alkyl, alkenyl, alkynyl, halo,            haloalkyl, haloalkenyl, haloalkynyl, cyano, nitro, aryl,            aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl,            cycloalkylalkenyl, cycloalkylalkynyl, heterocyclyl,            heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl,            heteroaryl, heteroarylalkyl, heteroarylalkenyl,            heteroarylalkynyl, —R¹⁵—OR¹⁴, —R¹⁵—OC(O)—R¹⁴, —R¹⁵—N(R¹⁴)₂,            —R¹⁵—C(O)R¹⁴, —R¹⁵—C(O)OR¹⁴, —R¹⁵—C(O)N(R¹⁴)₂,            —R¹⁵—O—R¹⁶—C(O)N(R¹⁴)₂, —R¹⁵—N(R¹⁴)C(O)OR¹⁴,            —R¹⁵—N(R¹⁴)C(O)R¹⁴, —R¹⁵—N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or            2), —R¹⁵—S(O)_(t)OR¹⁴ (where t is 1 or 2), —R¹⁵—S(O)_(p)R¹⁴            (where p is 0, 1 or 2), and —R¹⁵—S(O)_(t)N(R¹⁴)₂ (where t is            1 or 2), where each R¹⁴ is independently hydrogen, alkyl,            haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl,            heterocyclyl, heterocyclylalkyl, heteroaryl or            heteroarylalkyl, each R¹⁵ is independently a direct bond or            a straight or branched alkylene or alkenylene chain, and R¹⁶            is a straight or branched alkylene or alkenylene chain;    -   e) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, oxo,        and —R⁸—OR¹⁰; or    -   f) heteroarylalkenyl where the heteroaryl part of the        heteroarylakyl radical is optionally substituted with one or        more substituents selected from the group consisting of alkyl,        halo, haloalkyl, aryl and aralkyl;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   optionally, R⁶ and R⁷, together with the nitrogen to which they are    attached, form an optionally substituted N-heteroaryl or an    optionally substituted N-heterocyclyl;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl.

Another embodiment of the compounds of formula (Ib) are compounds offormula (Ib) wherein:

-   A is —C(O)—;-   R¹ is cycloalkyl optionally substituted with one or more    substituents selected from the group consisting of halo, haloalkyl,    alkyl, oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷, —R⁸—S(O)_(p)R¹⁰    (where p is 0, 1 or 2) and —R⁸—N(R⁶)R⁷;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is alkyl optionally substituted with one or more substituents    selected from the group consisting of halo, cyano, nitro, oxo,    thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,    —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,    —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t is 1    or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and —S(O)_(t)N(R¹⁴)₂    (where t is 1 or 2) where each R¹⁴ is independently hydrogen, alkyl,    haloalkyl, cycloalkyl, cycloalkylalkyl, aryl (optionally substituted    with one or more halo groups), aralkyl, heterocyclyl,    heterocylylalkyl, heteroaryl or heteroarylalkyl;-   or R³ is phenyl substituted with one or more substituents selected    from the group consisting of alkyl, halo, haloalkyl, nitro,    cycloalkyl, cycloalkylalkyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,    —R⁸—O—R⁸—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0,    1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,    —R⁸—N(R⁶)C(O)R¹⁰ and —R⁸—CN;-   or R³ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, oxo, and    —R⁸—OR¹⁰;-   each R⁶ and R⁷ is independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—NO₂, —R⁹—N(R¹³)₂,    —R⁹—C(O)OR¹³ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain or an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain or an    optionally substituted straight or branched alkenylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, or optionally substituted heteroarylalkyl.

Of this embodiment, a specific embodiment is a compound of formula (Ib)selected from the group consisting of:

-   3-amino-1-(4-(tert-butoxy)phenyl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2-yl)amino]-1H-1,2,4-triazole;-   3-amino-1-(3-(tert-butoxy)phenyl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2-yl)amino]-1H-1,2,4-triazole;-   3-amino-1-(4-(dimethylamino)phenyl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2-yl)amino]-1H-1,2,4-triazole;-   3-amino-1-(3-(dimethylamino)phenyl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2-yl)amino]-1H-1,2,4-triazole;-   3-amino-1-(4-(iso-propoxy)phenyl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2-yl)amino]-1H-1,2,4-triazole;    and-   3-amino-1-(1H-indol-6-yl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2-yl)amino]-1H-1,2,4-triazole.

Another embodiment of the various aspects of the invention set forthabove in the Summary of the Invention are compounds of formula (Ib):

-   wherein:-   A is —C(O)O—, or —C(O)N(R⁶)—;-   R¹ is one of the following:    -   a) aryl substituted with one or more substituents selected from        the group consisting of halo, haloalkyl, alkyl, optionally        substituted heteroaryl, optionally substituted heterocyclyl,        —R⁸—OR¹⁰, —R⁶—O—R⁸—OR¹⁰, —R⁸—O—R⁸—O—R⁸—OR¹⁰, —R⁸—O—R⁸—CN,        —R⁸—O—R⁸—C(O)OR¹⁰, —R⁸—O—R⁸—C(O)N(R⁶)R⁷, —R⁸—O—R⁸—S(O)_(p)R⁶        (where p is 0, 1 or 2), —R⁸—O—R⁸—N(R⁶)R⁷,        —R⁸—O—R⁸—C(NR¹¹)N(R¹¹)H, and —R⁸—N(R⁶)C(O)R¹⁰; or    -   b) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, halo,        oxo, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁶)R⁷;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is one of the following:    -   a) alkyl optionally substituted with one or more substituents        selected from the group consisting of halo, cyano, nitro, oxo,        thioxo, trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,        —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)R¹⁴,        —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴ (where t        is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2), and        —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is        independently hydrogen, alkyl, haloalkyl, cycloalkyl,        cycloalkylalkyl, aryl (optionally substituted with one or more        halo groups), aralkyl, heterocyclyl, heterocylylalkyl,        heteroaryl or heteroarylalkyl;    -   b) cycloalkyl optionally substituted with one or more        substituents selected from the group consisting of —R⁸—OR¹⁰,        alkyl, halo, haloalkyl, aryl, and aralkyl;    -   c) aryl substituted with one or more substituents selected from        the group consisting of alkyl, halo, haloalkyl, nitro,        cycloalkyl, cycloalkylalkyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰,        —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷,        —S(O)_(p)R⁶ (where p is 0, 1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is        1 or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰ and —R⁸—CN;    -   d) aralkyl, wherein:        -   (1) the alkyl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of halo, cyano, nitro, oxo, thioxo,            trimethylsilanyl, —OR¹⁴, —OC(O)—R¹⁴, —N(R¹⁴)₂, —C(O)R¹⁴,            —C(O)OR¹⁴, —C(O)N(R¹⁴)₂, —N(R¹⁴)C(O)OR¹⁴, —N(R¹⁴)C(O)_(R)            ¹⁴, —N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or 2), —S(O)_(t)OR¹⁴            (where t is 1 or 2), —S(O)_(p)R¹⁴ (where p is 0, 1 or 2),            and —S(O)_(t)N(R¹⁴)₂ (where t is 1 or 2) where each R¹⁴ is            independently hydrogen, alkyl, haloalkyl, cycloalkyl,            cycloalkylalkyl, aryl (optionally substituted with one or            more halo groups), aralkyl, heterocyclyl, heterocylylalkyl,            heteroaryl or heteroarylalkyl; and        -   (2) the aryl part of the aralkyl radical is optionally            substituted with one or more substituents selected from the            group consisting of alkyl, alkenyl, alkynyl, halo,            haloalkyl, haloalkenyl, haloalkynyl, cyano, nitro, aryl,            aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl,            cycloalkylalkenyl, cycloalkylalkynyl, heterocyclyl,            heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl,            heteroaryl, heteroarylalkyl, heteroarylalkenyl,            heteroarylalkynyl, —R¹⁵—OR¹⁴, —R¹⁵—OC(O)—R¹⁴, —R¹⁵—N(R¹⁴)₂,            —R¹⁵—C(O)R¹⁴, —R¹⁵—C(O)OR¹⁴, —R¹⁵—C(O)N(R¹⁴)₂,            —R¹⁵—O—R¹⁶—C(O)N(R¹⁴)₂, —R¹⁵—N(R¹⁴)C(O)OR¹⁴,            —R¹⁵—N(R¹⁴)C(O)R¹⁴, —R¹⁵—N(R¹⁴)S(O)_(t)R¹⁴ (where t is 1 or            2), —R¹⁵—S(O)_(t)OR¹⁴ (where t is 1 or 2), —R¹⁵—S(O)_(p)R¹⁴            (where p is 0, 1 or 2), and —R¹⁵—S(O)_(t)N(R¹⁴)₂ (where t is            1 or 2), where each R¹⁴ is independently hydrogen, alkyl,            haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl,            heterocyclyl, heterocyclylalkyl, heteroaryl or            heteroarylalkyl, each R¹⁵ is independently a direct bond or            a straight or branched alkylene or alkenylene chain, and R¹⁶            is a straight or branched alkylene or alkenylene chain;    -   e) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, oxo,        and —R⁸—OR¹⁰; or    -   f) heteroarylalkenyl where the heteroaryl part of the        heteroarylakyl radical is optionally substituted with one or        more substituents selected from the group consisting of alkyl,        halo, haloalkyl, aryl and aralkyl;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted aralkenyl, optionally    substituted aralkynyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted    cycloalkylalkenyl, optionally substituted cycloalkylalkynyl,    optionally substituted heterocyclyl, optionally substituted    heterocyclylalkyl, optionally substituted heterocyclylalkenyl,    optionally substituted heterocyclylalkynyl, optionally substituted    heteroaryl, optionally substituted heteroarylalkyl, optionally    substituted heteroarylalkenyl, optionally substituted    heteroarylalkynyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain, an optionally substituted straight or branched alkenylene    chain and an optionally substituted straight or branched alkynylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain, an    optionally substituted straight or branched alkenylene chain and an    optionally substituted straight or branched alkynylene chain; and-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,    haloalkynyl, optionally substituted aryl, optionally substituted    aralkyl, optionally substituted aralkenyl, optionally substituted    aralkynyl, optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted cycloalkylalkenyl,    optionally substituted cycloalkylalkynyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted heterocyclylalkenyl, optionally substituted    heterocyclylalkynyl, optionally substituted heteroaryl, optionally    substituted heteroarylalkyl, optionally substituted    heteroarylalkenyl, optionally substituted heteroarylalkynyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Another embodiment of the compounds of formula (Ib) are compounds offormula (Ib) wherein:

-   A is —C(O)O—, or —C(O)N(R⁶)—;-   R¹ is one of the following:    -   a) aryl substituted with one or more substituents selected from        the group consisting of halo, haloalkyl, alkyl, optionally        substituted heteroaryl, optionally substituted heterocyclyl,        —R⁸—OR¹⁰, —R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—CN,        —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶        (where p is 0, 1 or 2), —R⁸—O—R⁹—N(R⁶)R⁷,        —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and —R⁸—N(R⁶)C(O)R¹⁰; or    -   b) heteroaryl optionally substituted with one or more        substituents selected from the group consisting of alkyl, halo,        oxo, —R⁶—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—C(O)N(R⁶)R⁷ and —R⁸—N(R⁶)R⁷;-   R², R⁴ and R⁵ are each hydrogen;-   R³ is cycloalkyl optionally substituted with one or more    substituents selected from the group consisting of —R⁸—OR¹⁰, alkyl,    halo, haloalkyl, aryl, and aralkyl;-   or R³ is phenyl substituted with one or more substituents selected    from the group consisting of alkyl, halo, haloalkyl, nitro,    cycloalkyl, cycloalkylalkyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰,    —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0,    1 or 2), —S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷,    —R⁸—N(R⁶)C(O)R¹⁰, and —R⁸—CN;-   or R³ is heteroaryl optionally substituted with one or more    substituents selected from the group consisting of alkyl, oxo, and    —R⁸—OR¹⁰;-   R⁶ and R⁷ are each independently selected from the group consisting    of hydrogen, alkyl, haloalkyl, hydroxyalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    cycloalkyl, optionally substituted cycloalkylalkyl, optionally    substituted heterocyclyl, optionally substituted heterocyclylalkyl,    optionally substituted heteroaryl, optionally substituted    heteroarylalkyl, —R⁹—OR¹⁰, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,    —R⁹—C(O)OR¹³ and —R⁹—C(O)N(R¹⁰)₂;-   each R⁸ is independently selected from the group consisting of a    direct bond, an optionally substituted straight or branched alkylene    chain or an optionally substituted straight or branched alkenylene    chain;-   each R⁹ is independently selected from the group consisting of an    optionally substituted straight or branched alkylene chain or an    optionally substituted straight or branched alkenylene chain;-   each R¹⁰ is independently selected from the group consisting of    hydrogen, alkyl, haloalkyl, optionally substituted aryl, optionally    substituted aralkyl, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    heteroaryl, or optionally substituted heteroarylalkyl; and-   each R¹¹ is hydrogen, alkyl, cyano, nitro or —OR¹⁰.

Of this embodiment, a specific embodiment is a compound of formula (Ib)selected from the group consisting of:

-   3-amino-5-(1,4-benzodioxan-6-yl)amino-1-methoxycarbonyl-1H-1,2,4-triazole;-   5-[4-(acetyl(methyl)amino)phenyl]amino-3-amino-N-(1,3-benzodioxol-5-yl)-1H-1,2,4-triazole-1-carboxamide;-   5-[4-(acetyl(methyl)amino)phenyl]amino-3-amino-N-cyclopentyl-1H-1,2,4-triazole-1-carboxamide;-   3-amino-N-(4-(butoxy)phenyl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   3-amino-N-(4-(methyl)phenyl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   3-amino-N-(4-(methoxy)phenyl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   3-[4-(acetyl(methyl)amino)phenyl]amino-3-amino-N-cyclohexyl-1H-1,2,4-triazole-1-carboxamide;-   3-amino-N-(3-(methyl)phenyl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   3-amino-N-(3,5-dimethoxyphenyl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   3-amino-N-cyclohexyl-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;-   3-amino-N-cyclopentyl-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide;    and-   3-amino-N-(1,3-benzodioxol-5-yl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide.

Another embodiment of the various aspects of the invention set forthabove in the Summary of the Invention is the group of compounds offormula (Ia) and compounds of formula (Ib) which does not include thefollowing compounds (identified by their unique Chemical AbstractsRegistry number:

110984-61-7; 324074-12-6; 324074-13-7; 324074-14-8; 324074-15-9;324074-16-0; 324074-17-1; 324074-18-2; 324074-19-3; 324074-20-6;324074-21-7; 324074-22-8; 324074-23-9; 324074-24-0; 324074-25-1;324074-28-4; 324074-29-5; 324074-30-8; 324074-31-9; 324074-32-0;324074-33-1; 324074-34-2; 324074-35-3; 324074-36-4; 324074-38-6;324074-39-7; 324074-41-1; 324074-42-2; 324074-43-3; 324074-44-4;324074-45-5; 324074-46-6; 324074-47-7; 324074-48-8; 324074-50-2;324074-51-3; 324074-52-4; 443798-64-9; 443798-65-0; 443798-66-1;443798-67-2; 443798-68-3; 443798-69-4; 443798-70-7; 443798-71-8;443798-72-9; 443798-73-0; 443798-74-1; 443798-87-6; 443798-88-7;443798-89-8; 443798-90-1; 443798-91-2; 443798-92-3; 443798-93-4;443798-96-7; 443798-95-6; 443798-94-5; 443798-97-8; 443798-98-9;443798-99-0; 443799-10-8; 443799-12-0; 443799-14-2; 443799-16-4;443799-18-6; 503546-63-2; 503546-65-4; 700811-45-6; 700812-30-2;700812-68-6; 700812-69-7; 863030-86-8; 863030-85-7; 863030-84-6;863030-77-7; 863030-76-6; 863030-74-4; 863030-87-9; 863030-83-5;863030-81-3; and 863030-79-9.

Another embodiment of the various aspects of the invention set forthabove in the Summary of the Invention is the group of compounds offormula (Ia) and compounds of formula (Ib) which does not include thefollowing compounds:

5-amino-N-benzyl-3-(pyridin-3-ylamino)-1H-1,2,4-triazole-1-carboxamide;5-amino-N-(2-chlorophenyl)-3-(pyridin-3-ylamino)-1H-1,2,4-triazole-1-carboxamide;5-amino-N-(3-chlorophenyl)-3-(pyridin-3-ylamino)-1H-1,2,4-triazole-1-carboxamide;3-amino-N-(2-chlorophenyl)-5-(pyridin-3-ylamino)-1H-1,2,4-triazole-1-carboxamide;and5-amino-N-(4-methylphenyl)-3-(pyridin-3-ylamino)-1H-1,2,4-triazole-1-carboxamide.

Other embodiments of the invention are the pharmaceutical compositions,as set forth above in the Summary of the Invention, wherein thecompounds of formula (Ia) or the compounds of formula (Ib) therein areas set forth above in the embodiments of the compound of formula (Ia) orthe compound of formula (Ib).

Other embodiments of the invention are the methods of treating a diseaseor condition associated with Axl catalytic activity in a mammal, as setforth above in the Summary of the Invention, wherein the compounds offormula (Ia) or the compounds of formula (Ib) therein are as set forthabove in the embodiments of the compound of formula (Ia) or the compoundof formula (Ib).

Another embodiment of the invention are those methods of treating adisease or condition associated with Axl catalytic activity byadministering to the mammal a therapeutically effective amount of acompound of formula (I), as set forth above in the Summary of theInvention, wherein the disease or condition is selected from the groupconsisting of rheumatoid arthritis, vascular disease/injury (includingbut not limited to restenosis, atherosclerosis and thrombosis),psoriasis, visual impairment due to macular degeneration, diabeticretinopathy or retinopathy of prematurity, kidney disease (including butnot limited to glomerulonephritis, diabetic nephropathy and renaltransplant rejection), osteoarthritis and cataracts.

Another embodiment of the invention are those methods of treating adisease or condition associated with Axl catalytic activity byadministering to the mammal a therapeutically effective amount of acompound of formula (I), as set forth above in the Summary of theInvention, wherein the disease or condition is selected from the groupconsisting of breast carcinoma, renal carcinoma, endometrial carcinoma,ovarian carcinoma, thyroid carcinoma, non-small cell lung carcinoma,uveal melanoma, myeloid leukemia and lymphoma.

Another embodiment of the invention are those methods of treating adisease or condition associated with Axl catalytic activity byadministering to the mammal of therapeutically effective amount of acompound of formula (I), as set forth above in the Summary of theInvention, wherein the disease or condition is endometriosis.

Specific embodiments of the invention are described in more detail belowin the following sections.

Utility and Testing of the Compounds of the Invention

The oncogenic RTK, Axl, was recently identified, using aretroviral-based functional genetic screening protocol, as a regulatorof haptotactic migration, which is a key event in angiogenesis. Axlinhibition by RNAi-mediated silencing blocked endothelial cellmigration, proliferation and in vitro tube formation. Theseobservations, which were disclosed at the American Association CancerResearch General Meeting, Apr. 16-20, 2005, Anaheim, Calif., and The 7thAnnual Symposium on Anti-Angiogenic Agents, Feb. 10-13, 2005, San Diego,Calif.; (Requirement for The Receptor Tyrosine Kinase Axl inAngiogenesis and Tumor Growth, Holland, S. J. Powell, M. J., Franci, C.,Chan, E., Friera, A. M., Atchison, R., Xu, W., McLaughlin, J., Swift, S.E., Pali, E., Yam, G., Wong, S., Xu, X., Hu, Y., Lasaga, J., Shen, M.,Yu, S., Daniel, R., Hitoshi, Y., Bogenberger, J., Nor, J. E., Payan, D.G and Lorens, J. B), were substantiated by an in vivo study whichdemonstrated that stable, shRNAi-mediated Axl knockdown impairedformation of functional human blood vessels in a mouse model of humanangiogenesis. These observations were published in a peer reviewedjournal (Holland S J, Powell M J, Franci C, Chan E W, Friera A M,Atchison R E, McLaughlin J, Swift S E, Pali E S, Yam G, Wong S, LasagaJ, Shen M R, Yu S, Xu W, Hitoshi Y, Bogenberger J, Nor J E, Payan D G,Lorens J B. “Multiple roles for the receptor tyrosine kinase axl intumor formation.” Cancer Res. (2005) Vol 65 pp 9294-303. Theseobservations are also disclosed in U.S. Published Patent Application2005/0118604 and European Patent Application 1 563 094, the disclosuresof which are incorporated in full by reference. Axl signaling,therefore, impacts multiple functions required for neovascularization invitro, and regulates angiogenesis in vivo. Regulation of thesepro-angiogenic processes required the catalytic activity of Axl. Thus,Axl-mediated angiogenic stimulation would be amenable to modulation by asmall molecule inhibitor of Axl catalytic activity.

The compounds of the invention are small molecule inhibitors of Axlcatalytic activity, and are therefore useful in treating diseases andconditions which are associated with Axl catalytic activity includingthose diseases and conditions which are characterized by angiogenesisand/or cell proliferation. Such diseases and conditions include, but arenot limited to, solid tumors, including, but not limited to, breast,renal, endometrial, ovarian, thyroid, non-small cell lung carcinoma anduveal melanoma; liquid tumors, including but not limited to, leukemias(particularly myeloid leukemias) and lymphomas; endometriosis, vasculardisease/injury (including but not limited to restenosis, atherosclerosisand thrombosis), psoriasis; visual impairment due to maculardegeneration; diabetic retinopathy and retinopathy of prematurity;kidney disease (including but not limited to glomerulonephritis,diabetic nephropathy and renal transplant rejection), rheumatoidarthritis; osteoarthritis and cataracts.

The following animal models provide guidance to one of ordinary skill inthe art in testing the compounds of the invention for their use intreating the disease or condition indicated.

The compounds of the invention may be tested for their use in treatingleukemias and lymphomas by testing the compounds in the xenograft inSCID mouse model using human Axl-expressing cancer cell lines including,but not limited to, HeLa, MDA-MB-231, SK-OV-3, OVCAR-8, DU145 and H1299.

The compounds of the invention may be tested for their use in treatingleukemias in the xenograft in SCID mouse model using humanAxl-expressing AML and CML leukemia cell lines.

The compounds of the invention may be tested for their use in treatingendometriosis by using the syngenic mouse model of endometriosis (seeSomigliana, E. et al., “Endometrial ability to implant in ectopic sitescan be prevented by interleukin-12 in a murine model of endometriosis”,Hum. Reprod. (1999), Vol. 14, NO. 12, pp. 2944-50). The compounds mayalso be tested for their use in treating endometriosis by using the ratmodel of endometriosis (see Lebovic, D. I. et al., “Peroxisomeproliferator-activated receptor-gamma induces regression of endometrialexplants in a rat model of endometriosis”, Fertil. Steril. (2004), 82Suppl 3, pp. 1008-13).

The compounds of the invention may be tested for their use in treatingrestenosis by using the balloon-injured rate carotid artery model (seeKim, D. W. et al., “Novel oral formulation of paclitaxel inhibitsneointimal hyperplasia in a rat carotid artery injury model”,Circulation (2004), Vol. 109, No. 12, pp. 1558-63, Epub 2004 Mar. 8).

The compounds of the invention may also be tested for their use intreating restenosis by using the percutaneous transluminal coronaryangioplasty in apoE deficient mouse model (see von der Thusen, J. H. etal., “Adenoviral transfer of endothelial nitric oxide synthaseattenuates lesion formation in a novel murine model of postangioplastyrestenosis”, Arterioscler. Thromb. Vasc. Biol. (2004), Vol. 24, No. 2,pp. 357-62).

The compounds of the invention may be tested for their use in treatingatherosclerosis/thrombosis in the ApoE deficient mouse model (seeNakashima, Y. et al., “ApoE-deficient mice develop lesions of all phasesof atherosclerosis throughout the arterial tree”, Arterioscler. Thromb.(1994), Vol. 14, No. 1, pp. 133-40).

The compounds of the invention may also be tested for their use intreating thrombosis using the collagen-epinephrin-induced pulmonarythromboembolism model and the stasis induced venous thrombosis model(see Angelillo-Scherrer A. et al., “Role of Gas6 receptors in plateletsignaling during thrombus stabilization and implications forantithrombotic therapy”, J Clin Invest. (2005) Vol 115 pp 237-46).

The compounds of the invention may be tested for their use in treatingpsoriasis by using the SCID mouse model or the human skin model ofpsoriasis (see Nickoloff, B. J. et al., “Severe combinedimmunodeficiency mouse and human psoriatic skin chimeras. Validation ofa new animal model”, Am. J. Pathol. (1995), Vol. 146, No. 3, pp. 580-8).

The compounds of the invention may be tested for their use in treatingage-related macular degeneration or diabetic retinopathy by using therat corneal angiogenesis model (see Sarayba M A, Li L, Tungsiripat T,Liu N H, Sweet P M, Patel A J, Osann K E, Chittiboyina A, Benson S C,Pershadsingh H A, Chuck R S. Inhibition of corneal neovascularization bya peroxisome proliferator-activated receptor-gamma ligand. Exp Eye Res.2005 March; 80(3):435-42) or the laser-induced mouse choroidalneovasculation model (see Bora, P. S., et al., “Immunotherapy forchoroidal neovascularization in a laser-induced mouse model simulatingexudative (wet) macular degeneration”, Proc. Natl. Acad. Sci. U.S.A.(2003), Vol. 100, No. 5, pp. 2679-84, Epub 2003 Feb. 14).

The compounds of the invention may be tested for their use in treatingretinopathy of prematurity in the mouse retinopathy of prematurity model(see Smith, L. E. et al., “Oxygen-induced retinopathy in the mouse”,Invest. Ophthalmol. Vis. Sci. (1994), Vol. 35, No. 1, pp. 101-11).

The compounds of the invention may be tested for their use in treatingglomerulonephritis or diabetic nephropathy in the ratanti-Thy1.1-induced experimental mesengial proliferativeglomerulonephritis model (see Smith, L. E. et al, cited above).

The compounds of the invention may be tested for their use in treatingrenal transplant rejection by using a rat model of chronic renaltransplant rejection (see Yin, J. L. et al., “Expression of growtharrest-specific gene 6 and its receptors in a rat model of chronic renaltransplant rejection”, Transplantation (2002), Vol. 73, No. 4, pp.657-60).

The compounds of the invention may be tested for their use in treatingrheumatoid arthritis by using the CAIA mouse model (see Phadke, K. etal., “Evaluation of the effects of various anti-arthritic drugs on typeII collagen-induced mouse arthritis model”, Immunopharmacology (1985)Vol. 10, No. 1, pp. 51-60).

The compounds of the invention may be tested for their use in treatingosteoarthritis by using the STR/ORT mouse model (see Brewster, M. etal., “Ro 32-3555, an orally active collagenase selective inhibitor,prevents structural damage in the STR/ORT mouse model ofosteoarthritis”, Arthritis. Rheum. (1998), Vol. 41, No. 9, pp. 1639-44).

The compounds of the invention may be tested for their use in treatingcataracts by using the H₂O₂-induced model (see Kadoya, K. et al., “Roleof calpain in hydrogen peroxide induced cataract”, Curr. Eye Res.(1993), Vol. 12, No. 4, pp. 341-6) or the Emory mouse model (see Sheets,N. L. et al., “Cataract- and lens-specific upregulation of ARK receptortyrosine kinase in Emory mouse cataract”, Invest. Ophthalmol. Vis. Sci.(2002), Vol. 43, No. 6, pp. 1870-5).

Pharmaceutical Compositions of the Invention and Administration

Administration of the compounds of the invention, or theirpharmaceutically acceptable salts, in pure form or in an appropriatepharmaceutical composition, can be carried out via any of the acceptedmodes of administration of agents for serving similar utilities. Thepharmaceutical compositions of the invention can be prepared bycombining a compound of the invention with an appropriatepharmaceutically acceptable carrier, diluent or excipient, and may beformulated into preparations in solid, semi-solid, liquid or gaseousforms, such as tablets, capsules, powders, granules, ointments,solutions, suppositories, injections, inhalants, gels, microspheres, andaerosols. Typical routes of administering such pharmaceuticalcompositions include, without limitation, oral, topical, transdermal,inhalation, parenteral, sublingual, buccal, rectal, vaginal, andintranasal. The term parenteral as used herein includes subcutaneousinjections, intravenous, intramuscular, intrasternal injection orinfusion techniques. Pharmaceutical compositions of the invention areformulated so as to allow the active ingredients contained therein to bebioavailable upon administration of the composition to a patient.Compositions that will be administered to a subject or patient take theform of one or more dosage units, where for example, a tablet may be asingle dosage unit, and a container of a compound of the invention inaerosol form may hold a plurality of dosage units. Actual methods ofpreparing such dosage forms are known, or will be apparent, to thoseskilled in this art; for example, see Remington: The Science andPractice of Pharmacy, 20th Edition (Philadelphia College of Pharmacy andScience, 2000). The composition to be administered will, in any event,contain a therapeutically effective amount of a compound of theinvention, or a pharmaceutically acceptable salt thereof, for treatmentof a disease or condition of interest in accordance with the teachingsof this invention.

A pharmaceutical composition of the invention may be in the form of asolid or liquid. In one aspect, the carrier(s) are particulate, so thatthe compositions are, for example, in tablet or powder form. Thecarrier(s) may be liquid, with the compositions being, for example, anoral oil, injectable liquid or an aerosol, which is useful in, forexample, inhalatory administration.

When intended for oral administration, the pharmaceutical composition ispreferably in either solid or liquid form, where semi-solid,semi-liquid, suspension and gel forms are included within the formsconsidered herein as either solid or liquid.

As a solid composition for oral administration, the pharmaceuticalcomposition may be formulated into a powder, granule, compressed tablet,pill, capsule, chewing gum, wafer or the like form. Such a solidcomposition will typically contain one or more inert diluents or ediblecarriers. In addition, one or more of the following may be present:binders such as carboxymethylcellulose, ethyl cellulose,microcrystalline cellulose, gum tragacanth or gelatin; excipients suchas starch, lactose or dextrins, disintegrating agents such as alginicacid, sodium alginate, Primogel, corn starch and the like; lubricantssuch as magnesium stearate or Sterotex; glidants such as colloidalsilicon dioxide; sweetening agents such as sucrose or saccharin; aflavoring agent such as peppermint, methyl salicylate or orangeflavoring; and a coloring agent.

When the pharmaceutical composition is in the form of a capsule, forexample, a gelatin capsule, it may contain, in addition to materials ofthe above type, a liquid carrier such as polyethylene glycol or oil.

The pharmaceutical composition may be in the form of a liquid, forexample, an elixir, syrup, solution, emulsion or suspension. The liquidmay be for oral administration or for delivery by injection, as twoexamples. When intended for oral administration, preferred compositioncontain, in addition to the present compounds, one or more of asweetening agent, preservatives, dye/colorant and flavor enhancer. In acomposition intended to be administered by injection, one or more of asurfactant, preservative, wetting agent, dispersing agent, suspendingagent, buffer, stabilizer and isotonic agent may be included.

The liquid pharmaceutical compositions of the invention, whether they besolutions, suspensions or other like form, may include one or more ofthe following adjuvants: sterile diluents such as water for injection,saline solution, preferably physiological saline, Ringer's solution,isotonic sodium chloride, fixed oils such as synthetic mono ordiglycerides which may serve as the solvent or suspending medium,polyethylene glycols, glycerin, propylene glycol or other solvents;antibacterial agents such as benzyl alcohol or methyl paraben;antioxidants such as ascorbic acid or sodium bisulfite; chelating agentssuch as ethylenediaminetetraacetic acid; buffers such as acetates,citrates or phosphates and agents for the adjustment of tonicity such assodium chloride or dextrose. The parenteral preparation can be enclosedin ampoules, disposable syringes or multiple dose vials made of glass orplastic. Physiological saline is a preferred adjuvant. An injectablepharmaceutical composition is preferably sterile.

A liquid pharmaceutical composition of the invention intended for eitherparenteral or oral administration should contain an amount of a compoundof the invention such that a suitable dosage will be obtained.Typically, this amount is at least 0.01% of a compound of the inventionin the composition. When intended for oral administration, this amountmay be varied to be between 0.1 and about 70% of the weight of thecomposition. Preferred oral pharmaceutical compositions contain betweenabout 4% and about 75% of the compound of the invention. Preferredpharmaceutical compositions and preparations according to the presentinvention are prepared so that a parenteral dosage unit contains between0.01 to 10% by weight of the compound prior to dilution of theinvention.

The pharmaceutical composition of the invention may be intended fortopical administration, in which case the carrier may suitably comprisea solution, emulsion, ointment or gel base. The base, for example, maycomprise one or more of the following: petrolatum, lanolin, polyethyleneglycols, bee wax, mineral oil, diluents such as water and alcohol, andemulsifiers and stabilizers. Thickening agents may be present in apharmaceutical composition for topical administration. If intended fortransdermal administration, the composition may include a transdermalpatch or iontophoresis device. Topical formulations may contain aconcentration of the compound of the invention from about 0.1 to about10% w/v (weight per unit volume).

The pharmaceutical composition of the invention may be intended forrectal administration, in the form, for example, of a suppository, whichwill melt in the rectum and release the drug. The composition for rectaladministration may contain an oleaginous base as a suitablenonirritating excipient. Such bases include, without limitation,lanolin, cocoa butter and polyethylene glycol.

The pharmaceutical composition of the invention may include variousmaterials, which modify the physical form of a solid or liquid dosageunit. For example, the composition may include materials that form acoating shell around the active ingredients. The materials that form thecoating shell are typically inert, and may be selected from, forexample, sugar, shellac, and other enteric coating agents.Alternatively, the active ingredients may be encased in a gelatincapsule.

The pharmaceutical composition of the invention in solid or liquid formmay include an agent that binds to the compound of the invention andthereby assists in the delivery of the compound. Suitable agents thatmay act in this capacity include a monoclonal or polyclonal antibody, aprotein or a liposome.

The pharmaceutical composition of the invention may consist of dosageunits that can be administered as an aerosol. The term aerosol is usedto denote a variety of systems ranging from those of colloidal nature tosystems consisting of pressurized packages. Delivery may be by aliquefied or compressed gas or by a suitable pump system that dispensesthe active ingredients. Aerosols of compounds of the invention may bedelivered in single phase, bi-phasic, or tri-phasic systems in order todeliver the active ingredient(s). Delivery of the aerosol includes thenecessary container, activators, valves, subcontainers, and the like,which together may form a kit. One of ordinary skill in the art, withoutundue experimentation may determine preferred aerosols.

The pharmaceutical compositions of the invention may be prepared bymethodology well known in the pharmaceutical art. For example, apharmaceutical composition intended to be administered by injection canbe prepared by combining a compound of the invention with sterile,distilled water so as to form a solution. A surfactant may be added tofacilitate the formation of a homogeneous solution or suspension.Surfactants are compounds that non-covalently interact with the compoundof the invention so as to facilitate dissolution or homogeneoussuspension of the compound in the aqueous delivery system.

The compounds of the invention, or their pharmaceutically acceptablesalts, are administered in a therapeutically effective amount, whichwill vary depending upon a variety of factors including the activity ofthe specific compound employed; the metabolic stability and length ofaction of the compound; the age, body weight, general health, sex, anddiet of the patient; the mode and time of administration; the rate ofexcretion; the drug combination; the severity of the particular disorderor condition; and the subject undergoing therapy. Generally, atherapeutically effective daily dose is (for a 70 kg mammal) from about0.001 mg/kg (i.e., 0.7 mg) to about 100 mg/kg (i.e., 7.0 gm); preferablya therapeutically effective dose is (for a 70 kg mammal) from about 0.01mg/kg (i.e., 7 mg) to about 50 mg/kg (i.e., 3.5 gm); more preferably atherapeutically effective dose is (for a 70 kg mammal) from about 1mg/kg (i.e., 70 mg) to about 25 mg/kg (i.e., 1.75 gm).

Compounds of the invention, or pharmaceutically acceptable derivativesthereof, may also be administered simultaneously with, prior to, orafter administration of one or more other therapeutic agents. Suchcombination therapy includes administration of a single pharmaceuticaldosage formulation which contains a compound of the invention and one ormore additional active agents, as well as administration of the compoundof the invention and each active agent in its own separatepharmaceutical dosage formulation. For example, a compound of theinvention and the other active agent can be administered to the patienttogether in a single oral dosage composition such as a tablet orcapsule, or each agent administered in separate oral dosageformulations. Where separate dosage formulations are used, the compoundsof the invention and one or more additional active agents can beadministered at essentially the same time, i.e., concurrently, or atseparately staggered times, i.e., sequentially; combination therapy isunderstood to include all these regimens.

Preparation of the Compounds of the Invention

The following Reaction Schemes illustrate methods to make compounds ofthis invention, i.e., compounds of formula (Ia) and compounds of formula(Ib):

where A, R¹, R², R³, R⁴ and R⁵ are described above in the Summary of theInvention, as isolated stereoisomers or tautomers thereof or mixturesthereof, or as pharmaceutically acceptable salts, hydrates, solvates,N-oxides or prodrugs thereof. It is understood that in the followingReaction Schemes, combinations of substituents and/or variables of thedepicted formulae are permissible only if such contributions result instable compounds.

It will also be appreciated by those skilled in the art that in theprocesses described below the functional groups of intermediatecompounds may need to be protected by suitable protecting groups. Suchfunctional groups include hydroxy, amino, mercapto and carboxylic acid.Suitable protecting groups for hydroxy include trialkylsilyl ordiarylalkylsilyl (for example, t-butyldimethylsilyl,t-butyldiphenylsilyl or trimethylsilyl), tetrahydropyranyl, benzyl, andthe like. Suitable protecting groups for amino, amidino and guanidinoinclude t-butoxycarbonyl, benzyloxycarbonyl, and the like. Suitableprotecting groups for mercapto include —C(O)—R″ (where R″ is alkyl, arylor arylalkyl), p-methoxybenzyl, trityl and the like. Suitable protectinggroups for carboxylic acid include alkyl, aryl or arylalkyl esters.

Protecting groups may be added or removed in accordance with standardtechniques, which are known to one of ordinary skill in the art and asdescribed herein.

The use of protecting groups is described in detail in Green, T. W. andP. G. M. Wuts, Protective Groups in Organic Synthesis (1999), 3rd Ed.,Wiley. As one of skill in the art would appreciate, the protecting groupmay also be a polymer resin such as a Wang resin, Rink resin or a2-chlorotrityl-chloride resin.

It will also be appreciated by those skilled in the art, although suchprotected derivatives of compounds of this invention may not possesspharmacological activity as such, they may be administered to a mammaland thereafter metabolized in the body to form compounds of theinvention which are pharmacologically active. Such derivatives maytherefore be described as “prodrugs”. All prodrugs of compounds of thisinvention are included within the scope of the invention.

It is understood that one of ordinary skill in the art would be able tomake the compounds of the invention by methods similar to the methodsdescribed herein or by methods known to one of ordinary skill in theart. It is also understood that one of ordinary skill in the art wouldbe able to make in a similar manner as described below other compoundsof formula (Ia) and formula (Ib) not specifically illustrated below byusing the appropriate starting components and modifying the parametersof the synthesis as needed. In general, starting components may beobtained from sources such as Sigma Aldrich, Lancaster Synthesis, Inc.,Maybridge, Matrix Scientific, TCI, and Fluorochem USA, etc, orsynthesized according to sources known to those skilled in the art (see,for example, Advanced Organic Chemistry: Reactions, Mechanisms, andStructure, 5th edition (Wiley, December 2000)) or prepared as describedin this invention. ¹H NMR spectra were recorded in CDCl₃, DMSO-d₆,CD₃OD, Acetone-d₆ with trimethylsilane (TMS) as internal reference usingGemini 300 MHz instrument. Reagents and solvents were purchased fromcommercial sources and used without further purification. Flash columnchromatography was conducted using silica gel (230-400 mesh) under apositive pressure of nitrogen. LCMS spectra for purity and mass wererecorded using Waters LCMS instruments. Deionized water was used todilute the reactions and wash the products. Brine used was prepared bydissolving sodium chloride into deionized water to saturation point.

In the following Reaction Schemes, the following common abbreviationsare used:

HOAt for 1-hydroxy-7-azabenzotriazole

Bn for benzyl

EDCl.HCl for 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride

^(i)Pr₂NEt for N,N-diisopropylethylamine

DMF for N,N-Dimethylformamide

rt for ambient temperature

MeOH for methanol

THF for tetrahydrofuran

TFA for trifluoroacetic acid

THP for tetrahydropyran

BOC for benzyloxycarbonyl

Pd(dba)₂ for bis(dibenzylideneacetone)palladium

EtOAc for ethyl acetate

2-PrOH for iso-propylalcohol, isopropanol or 2-propanol

Ph₂P(CH₂)₄PPh₂ for 1,4-bis(diphenylphosphino)butane

HOAc for acetic acid

Compounds (Ia-1) and (Ib-1), as set forth below in Reaction Scheme 1,are compounds of formula (Ia) and (Ib), as set forth above in theSummary of the Invention, and are prepared as illustrated below inReaction Scheme 1 where R^(1a) is one or more substituents selected fromthe group consisting of halo, haloalkyl, alkyl, optionally substitutedheteroaryl, optionally substituted heterocyclyl, —R⁸—OR¹⁰,—R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—CN, —R⁸—O—R⁹—C(O)OR¹⁰,—R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶ (where p is 0, 1 or 2),—R⁸—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and —R⁸—N(R⁶)C(O)R¹⁰, whereineach R⁶, R⁷, R⁸, R⁹, R¹⁰ and R¹¹ are as defined above in the Summary ofthe Invention and R³⁸ is one or more substituents selected from thegroup consisting of halo, haloalkyl, alkyl, optionally substitutedheteroaryl, optionally substituted heterocyclyl, —R⁸—OR¹⁰,—R⁸—O—R⁹—OR¹⁰—R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰,—R⁸—O—R⁹—C(O)N(R⁶)R⁷, —R⁸—O—R⁹—S(O)_(p)R⁶ (where p is 0, 1 or 2),—R⁸—O—R⁹—N(R⁶)R⁷, —R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and —R⁸—N(R⁶)C(O)R¹⁰ whereeach R⁶, R⁷, R⁸, R⁹, R¹⁰ and R¹¹ is as defined above in the Summary ofthe Invention:

In general, diphenylcyanocarbonimidate 1 (1.1 equiv) and appropriatelysubstituted aniline 2 (1 equiv) are stirred in isopropyl alcohol atambient temperature overnight. The diarylisourea product, 3, generallyprecipitates and isolation can be accomplished via filtration, washingwith an appropriate solvent, and drying. Hydrazine hydrate (2 equiv) isadded to a slurry of 3 in an alcohol or other appropriate solvent.Generally, the ring formation reaction occurs at ambient temperature andthe product triazole, 4, can be isolated by standard isolationtechniques. The 3,5-diamino-1,2,4-triazole, 4, is then acylated with anappropriately substituted benzoic acid 5 to provide a mixture of theacylated products, (Ia-1) and (Ib-1), which can be separated andisolated by standard separation and isolation techniques, such aschromatography.

Compounds (Ia-2), as set forth below in Reaction Scheme 1A, arecompounds of formula (Ia), as set forth above in the Summary of theInvention, and are prepared as illustrated below in Reaction Scheme 1A.For purposes of convenience, the minor product, i.e., the correspondingcompound of formula (Ib), is not illustrated in Reaction Scheme 1A, butit is understood that the compound is prepared as well by the methoddisclosed therein and is isolated and separated from compound (Ia-2) bystandard isolation and separation techniques.

Specifically, diphenylcyanocarbonimidate 1 (1.1 equiv) and aniline 2a (1equiv) were stirred in iso-propyl alcohol at ambient temperatureovernight. The white precipitate was filtered and washed with iso-propylalcohol and dried to yield 3a. Then hydrazine hydrate (2 equiv) wasadded to a slurry of 3a in methanol. After stirring at ambienttemperature overnight the solution was concentrated and the oily residuewas triturated with diethyl ether to remove impurities and give 4a as awhite solid. The 3,5-diamino-1,2,4-triazole compound 4a was thenacylated with benzoic acid 5a mediated by HOAt/EDCl.HCl and ^(i)Pr₂NEtin anhydrous DMF. The reaction mixture was diluted with ethyl acetateand washed with aqueous sodium bicarbonate. The organic layer wasseparated and concentrated. Purification of the residue by silica gelcolumn chromatography in 5% triethylamine/ethyl acetate gave5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(Ia-2), as a yellow solid (38% yield); ¹H-NMR (DMSO-d₆, 300 MHz) 9.01(s, 1H), 8.22 (d, J=8.7 Hz, 2H), 7.69 (br. s, 2H), 7.41 (d, J=8.7 Hz,2H), 7.04 (d, J=8.7 Hz, 2H), 6.82 (d, J=8.7 Hz, 2H), 4.78 (m, 1H), 3.98(br. s, 2H), 2.77 (br. s, 2H), 2.48 (m, 4H), 1.67 (m, 4H), 1.30 (d,J=6.0 Hz, 6H) ppm; MS (ES) 451.4 (M+H), 449.0 (M−H).

In a similar manner as described above in Reaction Scheme 1 and ReactionScheme 1A, the following compounds of formula (Ia) and formula (Ib) weremade with the appropriately substituted starting materials. The numberfollowing each compound below refers to its number in Tables 1-10, asdiscussed in more detail below.

5-Amino-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1-(4-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole(compound #1), as a yellow solid (52% yield); ¹H-NMR (DMSO-d₆, 300 MHz)9.03 (s, 1H), 8.17 (d, J=9.0 Hz, 2H), 7.72 (br. s, 2H), 7.41 (d, J=9.0Hz, 2H), 7.12 (d, J=9.0 Hz, 2H), 6.81 (d, J=9.0 Hz, 2H), 3.99 (t, J=5.6Hz, 2H), 2.80 (br. s, 2H), 2.55 (m, 4H), 1.69 (m, 4H), 1.41 (s, 9H) ppm;MS (ES) 465.2 (M+H), 463.3 (M−H).

5-Amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #2), as a yellow solid (65% yield); ¹H-NMR (DMSO-d₆, 300 MHz)8.97 (s, 1H), 8.25 (d, J=9.0 Hz, 2H), 7.63 (br. s, 2H), 7.44 (d, J=9.0Hz, 2H), 6.84 (d, J=9.3 Hz, 2H), 6.77 (d, J=9.3 Hz, 2H), 3.98 (t, J=6.1Hz, 2H), 2.60 (t, J=6.1 Hz, 2H), 2.42 (m, 4H), 1.49 (m, 4H), 1.38 (m,2H) ppm; MS (ES) 450.2 (M+H), 448.0 (M−H).

5-Amino-1-(1H-indol-5-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #3), ¹H-NMR (DMSO-d₆, 300 MHz) 11.48 (s, 1H), 9.03 (s, 1H),8.69 (s, 1H), 8.14 (s, 1H), 7.95 (d, J=8.4 Hz, 1H), 7.71 (s, 2H), 7.49(d, J=9.0 Hz, 2H), 7.46 (d, J=8.1 Hz, 1H), 6.81 (d, J=8.7 Hz, 2H), 6.62(s, 1H), 4.02 (t, J=5.6 Hz, 2H), 2.91 (t, J=5.6 Hz, 2H), 2.68 (m, 4H),1.72 (m, 4H) ppm; MS (ES) 432.9 (M+H), 430.5 (M−H).

5-Amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #4), ¹H-NMR (DMSO-d₆, 300 MHz) 8.96 (s, 1H), 8.24 (d, J=7.8Hz, 2H), 7.62 (s, 2H), 7.44 (d, J=7.8 Hz, 2H), 6.83 (d, J=7.8 Hz, 2H),6.76 (d, J=8.1 Hz, 2H), 3.99 (t, J=5.7 Hz, 2H), 3.03 (s, 6H), 2.81 (m,2H), 2.55 (m, 4H), 1.68 (m, 4H) ppm; MS (ES) 436.2 (M+H), 434.1 (M−H).

5-Amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #5), ¹H-NMR (DMSO-d₆, 300 MHz) 11.6 (s, 1H), 9.04 (s, 1H),8.50 (s, 1H), 8.13 (s, 1H), 7.85 (d, J=8.7 Hz, 1H), 7.73 (s, 2H), 7.63(d, J=8.7 Hz, 1H), 7.47 (d, J=8.7 Hz, 2H), 6.84 (d, J=8.4 Hz, 2H), 6.54(s, 1H), 4.02 (t, J=5.6 Hz, 2H), 2.93 (t, J=5.6 Hz, 2H), 2.69 (m, 4H),1.73 (m, 4H) ppm; MS (ES) 432.9 (M+H), 430.5 (M−H).

5-Amino-1-(1H-indol-2-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #6), ¹H-NMR (DMSO-d₆, 300 MHz) 11.91 (s, 1H), 9.15 (s, 1H),8.15 (s, 1H), 8.00 (s, 1H), 7.81 (s, 2H), 7.55 (d, J=8.4 Hz, 2H), 7.51(d, J=11.7 Hz, 1H), 7.29 (t, J=8.1 Hz, 1H), 7.10 (t, J=7.8 Hz, 1H), 6.95(d, J=8.7 Hz, 2H), 4.06 (t, J=5.6 Hz, 2H), 2.85 (t, J=5.6 Hz, 2H), 2.60(m, 4H), 1.71 (m, 4H) ppm; MS (ES) 432.9 (M+H), 430.5 (M−H).

5-Amino-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1-(3-(trifluoromethoxy)phenyl)carbonyl-1H-1,2,4-triazole(compound #7), ¹H-NMR (DMSO-d₆, 300 MHz) 9.11 (s, 1H), 8.21 (s, 1H),8.09 (d, J=7.2 Hz, 1H), 7.80 (s, 2H), 7.68 (m, 2H), 7.38 (d, J=9.0 Hz,2H), 6.75 (d, J=8.7 Hz, 2H), 3.96 (t, J=5.8 Hz, 2H), 2.75 (m, 2H), 2.49(m, 4H), 1.67 (m, 4H) ppm; MS (ES) 477.2 (M+H), 475.0 (M−H).

5-Amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[4-[3-(pyrrolidin-1-yl)propoxy]phenylamino]-1H-1,2,4-triazole(compound #8), ¹H-NMR (DMSO-d₆, 300 MHz) 8.96 (s, 1H), 8.25 (d, J=9.0Hz, 1H), 7.62 (s, 2H), 7.44 (d, J=9.0 Hz, 2H), 6.82 (d, J=9.3 Hz, 2H),6.77 (d, J=9.0 Hz, 2H), 3.93 (t, J=6.3 Hz, 2H), 3.30 (t, J=6.3 Hz, 2H),3.04 (s, 6H), 2.49 (m, 4H), 1.85 (quint, 2H), 1.68 (m, 4H) ppm; MS (ES)450.3 (M+H), 448.3 (M−H).

5-Amino-1-(3-methylphenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #9), ¹H-NMR (DMSO-d₆, 300 MHz) 9.05 (s, 1H), 8.04 (s, 1H),7.90 (d, J=7.2 Hz, 1H), 7.75 (s, 2H), 7.43 (m, 4H), 6.79 (d, J=8.4 Hz,2H), 3.96 (t, J=5.7 Hz, 2H), 2.72 (t, J=5.7 Hz, 2H), 2.49 (m, 4H), 2.42(s, 3H), 1.67 (m, 4H) ppm; MS (ES) 407.2 (M+H), 405.2 (M−H).

5-Amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-[3-(pyrrolidin-1-yl)propoxy]phenylamino]-1H-1,2,4-triazole(compound #10), ¹H-NMR (DMSO-d₆, 300 MHz) 9.02 (s, 1H), 8.24 (d, J=9.0Hz, 1H), 7.71 (s, 2H), 7.42 (d, J=9.3 Hz, 2H), 7.05 (d, J=9.0 Hz, 2H),6.82 (d, J=9.0 Hz, 2H), 4.78 (m, 1H), 3.93 (t, J=6.0 Hz, 2H), 3.31 (m,2H), 2.49 (m, 4H), 1.87 (m, 2H), 1.70 (m, 4H) 1.32 (d, J=5.7 Hz, 6H)ppm; MS (ES) 465.4 (M+H), 463.0 (M−H).

5-Amino-1-(3-(dimethylamino)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #11), ¹H-NMR (DMSO-d₆, 300 MHz) 9.04 (s, 1H), 7.74 (s, 2H),7.57 (m, 1H), 7.42 (d, J=9.0 Hz, 2H), 7.35 (m, 2H), 6.98 (dm, J=9.0 Hz,1H), 6.76 (d, J=9.0 Hz, 2H), 3.96 (t, J=6.0 Hz, 2H), 2.95 (s, 6H), 2.58(t, J=6.0 Hz, 2H), 2.42 (m, 4H), 1.48 (m, 4H), 1.38 (m, 2H) ppm; MS (ES)450.3 (M+H), 448.2 (M−H).

5-Amino-1-(4-methylphenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #12), ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (s, 1H), 8.09 (d, J=8.1Hz, 2H), 7.73 (s, 2H), 7.40 (d, J=9.0 Hz, 2H), 7.35 (d, J=−8.4 Hz, 2H),6.80 (d, J=8.4 Hz, 2H), 3.97 (t, J=5.7 Hz, 2H), 2.73 (t, J=5.7 Hz, 2H),2.49 (m, 4H), 2.41 (s, 3H), 1.66 (m, 4H) ppm; MS (ES) 407.3 (M+H), 405.1(M−H).

5-Amino-1-(1,3-benzodioxol-5-yl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #13), ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (s, 1H), 7.89 (d, J=7.5Hz, 1H), 7.73 (d, J=7.5 Hz, 1H), 7.72 (s, 2H), 7.39 (d, J=8.7 Hz, 2H),7.08 (d, J=8.1 Hz, 1H), 6.80 (d, J=8.4 Hz, 2H), 6.15 (s, 2H), 3.96 (t,J=5.4 Hz, 2H), 2.59 (t, J=5.4 Hz, 2H), 2.39 (m, 4H), 1.48 (m, 4H), 1.36(m, 2H) ppm; MS (ES) 451.3 (M+H), 449.5 (M−H).

5-Amino-1-(3-methoxyphenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #14), ¹H-NMR (DMSO-d₆, 300 MHz) 9.06 (s, 1H), 7.77 (s, 2H),7.68 (d, J=6.6 Hz, 1H), 7.46 (t, J=7.8 Hz, 2H), 7.40 (d, J=9.3 Hz, 2H),7.19 (d, J=7.5 Hz, 1H), 6.77 (d, J=9.0 Hz, 2H), 3.96 (t, J=5.4 Hz, 2H),2.75 (t, J=5.4 Hz, 2H), 2.49 (m, 4H), 1.67 (m, 4H) ppm; MS (ES) 423.2(M+H), 421.2 (M−H).

5-Amino-3-[4-[3-(pyrrolidin-1-yl)propoxy]phenylamino]-1-(4-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole(compound #15), ¹H-NMR (DMSO-d₆, 300 MHz) 9.02 (s, 1H), 8.17 (d, J=8.7Hz, 1H), 7.72 (s, 2H), 7.40 (d, J=8.7 Hz, 2H), 7.12 (d, J=8.7 Hz, 2H),6.79 (d, J=8.7 Hz, 2H), 3.91 (t, J=6.3 Hz, 2H), 2.49 (m, 2H), 2.41 (m,4H), 1.83 (quint, J=6.6 Hz, 2H), 1.66 (m, 4H) 1.41 (s, 9H) ppm; MS (ES)479.2 (M+H), 477.6 (M−H).

5-Amino-1-(1,3-benzodioxol-5-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #16), ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (s, 1H), 7.89 (dd, J=8.1,1.8 Hz, 1H), 7.74 (d, J=9.0 Hz, 1H), 7.72 (s, 2H), 7.40 (d, J=8.7 Hz,2H), 7.08 (d, J=8.4 Hz, 1H), 6.80 (d, J=8.7 Hz, 2H), 6.15 (s, 2H), 3.97(t, J=5.4 Hz, 2H), 2.75 (t, J=5.4 Hz, 2H), 2.43 (m, 4H), 1.67 (m, 4H)ppm; MS (ES) 437.2 (M+H), 435.1 (M−H).

5-Amino-1-(1,4-benzodioxan-6-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #17), ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (s, 1H), 7.80 (m, 2H),7.72 (s, 2H), 7.41 (d, J=7.2 Hz, 2H), 7.00 (d, J=8.1 Hz, 1H), 6.80 (d,J=8.1 Hz, 2H), 4.33 (s, 2H), 4.31 (s, 2H), 3.97 (t, J=5.4 Hz, 2H), 2.74(t, J=5.4 Hz, 2H), 2.43 (m, 4H), 1.66 (m, 4H) ppm; MS (ES) 451.3 (M+H),449.2 (M−H.

5-Amino-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1-(3-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole(compound #18), ¹H-NMR (DMSO-d₆, 300 MHz) 9.05 (s, 1H), 7.82 (d, J=7.5Hz, 1H), 7.77 (m, 3H), 7.47 (t, J=7.8 Hz, 1H), 7.39 (d, J=9.0 Hz, 2H),7.24 (dm, J=7.5 Hz, 1H), 6.76 (d, J=8.7 Hz, 2H), 3.97 (t, J=6.0 Hz, 2H),2.75 (t, J=6.0 Hz, 2H), 2.49 (m, 4H), 1.67 (m, 4H), 1.32 (s, 9H) ppm; MS(ES) 465.4 (M+H), 463.2 (M−H).

5-Amino-1-(3,5-(dimethoxy)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #19), ¹H-NMR (DMSO-d₆, 300 MHz) 9.07 (s, 1H), 7.77 (s, 2H),7.42 (d, J=8.7 Hz, 1H), 7.36 (s, 1H), 7.35 (s, 1H), 6.77 (d, J=8.7 Hz,2H), 6.75 (s, 1H), 3.97 (t, J=5.4 Hz, 2H), 3.80 (s, 6H), 2.61 (m, 2H),2.42 (m, 4H), 1.49 (m, 4H), 1.37 (m, 2H) ppm; MS (ES) 467.2 (M+H), 465.2(M−H).

5-Amino-1-(3-(dimethylamino)phenyl)carbonyl-3-[4-[3-(pyrrolidin-1-yl)propoxy]phenylamino]-1H-1,2,4-triazole(compound #20), ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (s, 1H), 7.74 (s, 2H),7.57 (s, 1H), 7.42 (d, J=9.0 Hz, 2H), 7.33 (m, 2H), 6.97 (dm, J=7.8 Hz,1H), 6.75 (d, J=9.0 Hz, 2H), 3.91 (t, J=6.3 Hz, 2H), 2.95 (s, 6H), 2.54(m, 2H), 2.49 (m, 4H), 1.84 (quint, J=6.3 Hz, 2H), 1.68 (m, 4H) ppm; MS(ES) 450.2 (M+H), 448.6 (M−H).

5-Amino-1-(3,4-(dimethoxy)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #21), ¹H-NMR (DMSO-d₆, 300 MHz) 9.06 (s, 1H), 7.99 (s, 1H),7.89 (d, J=7.6 Hz, 1H), 7.73 (s, 2H), 7.44 (d, J=8.7 Hz, 2H), 7.12 (d,J=7.6 Hz, 1H), 6.80 (d, J=8.7 Hz, 2H), 3.97 (t, J=5.4 Hz, 2H), 3.87 (s,3H), 3.82 (s, 3H), 2.59 (t, J=5.4 Hz, 2H), 2.40 (m, 4H), 1.48 (m, 4H),1.36 (m, 2H) ppm; MS (ES) 467.3 (M+H), 465.1 (M−H).

5-Amino-1-(3,5-(dimethoxy)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #22), ¹H-NMR (DMSO-d₆, 300 MHz) 9.07 (s, 1H), 7.77 (s, 1H),7.42 (d, J=8.1 Hz, 2H), 7.35 (s, 2H), 6.76 (d, J=7.8 Hz, 2H), 6.75 (s,1H), 3.96 (t, J=5.7 Hz, 2H), 3.80 (s, 6H), 2.72 (t, J=5.7 Hz, 2H), 2.49(m, 4H), 1.66 (m, 4H) ppm; MS (ES) 453.2 (M+H), 451.4 (M−H).

5-Amino-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1-(4-(trifluoromethoxy)phenyl)carbonyl-1H-1,2,4-triazole(compound #23), ¹H-NMR (DMSO-d₆, 300 MHz) 9.06 (s, 1H), 8.27 (d, J=8.4Hz, 2H), 7.78 (s, 2H), 7.54 (d, J=7.5 Hz, 2H), 7.37 (d, J=8.4 Hz, 2H),6.80 (d, J=8.7 Hz, 2H), 3.97 (m, 2H), 2.76 (m, 3H), 2.49 (m, 4H), 1.68(m, 4H) ppm; MS (ES) 477.4 (M+H), 475.4 (M−H).

5-Amino-3-[4-[3-(pyrrolidin-1-yl)propoxy]phenylamino]-1-(3-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole(compound #24), ¹H-NMR (DMSO-d₆, 300 MHz) 9.04 (s, 1H), 7.82 (d, J=7.8Hz, 1H), 7.78 (s, 1H), 7.76 (s, 2H), 7.46 (t, J=7.8 Hz, 1H), 7.38 (d,J=8.7 Hz, 2H), 7.23 (d, J=7.2 Hz, 1H), 6.75 (d, J=9.0 Hz, 2H), 3.90 (t,J=6.3 Hz, 2H), 2.46 (m, 2H), 2.40 (m, 4H), 1.82 (quint, J=6.3 Hz, 2H),1.66 (m, 4H), 1.32 (s, 9H) ppm; MS (ES) 479.4 (M+H), 477.4 (M−H).

5-Amino-1-(benzimidazol-6-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #25), ¹H-NMR (DMSO-d₆, 300 MHz) 9.07 (s, 1H), 8.63 (s, 1H),8.40 (s, 1H), 8.34 (s, 1H), 8.02 (d, J=8.7 Hz, 1H), 7.76 (s, 2H), 7.70(d, J=8.7 Hz, 1H), 7.45 (d, J=9.0 Hz, 2H), 6.81 (d, J=9.0 Hz, 2H), 4.04(t, J=5.7 Hz, 2H), 2.99 (t, J=5.7 Hz, 2H), 2.77 (m, 4H), 1.75 (m, 4H)ppm; MS (ES) 433.5 (M+H), 431.5 (M−H).

5-Amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-(piperidin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #26), ¹H-NMR (DMSO-d₆, 300 MHz) 8.93 (s, 1H), 8.24 (d, J=8.7Hz, 2H), 7.69 (s, 2H), 7.36 (d, J=8.7 Hz, 1H), 7.05 (d, J=8.7 Hz, 1H),6.82 (d, J=8.7 Hz, 2H), 4.78 (m, 1H), 2.97 (t, J=5.7 Hz, 4H), 1.60 (m,4H), 1.48 (m, 2H), 1.31 (d, J=5.7 Hz, 6H) ppm; MS (ES) 421.2 (M+H),419.3 (M−H).

5-Amino-1-(4-(methoxy)cyclohexyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #27), ¹H-NMR (DMSO-d₆, 300 MHz) 8.97 (s, 1H), 7.52 (s, 2H),7.44 (d, J=8.7 Hz, 2H), 6.82 (d, J=8.7 Hz, 2H), 3.98 (t, J=5.1 Hz, 2H),3.39 (s, 3H), 3.22 (m, 1H), 2.73 (t, J=5.1 Hz, 2H), 2.49 (m, 4H),2.07-1.45 (m, 13H) ppm; MS (ES) 429.3 (M+H), 427.2 (M−H); and

5-Amino-1-(6-(methyl)pyridin-3-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #28), ¹H-NMR (DMSO-d₆, 300 MHz) 8.88 (s, 1H), 8.32 (s, 1H),8.16 (s, 2H), 8.08 (d, J=6.6 Hz, 1H), 7.37 (d, J=8.7 Hz, 2H), 7.32 (d,J=7.5 Hz, 1H), 6.75 (d, J=9.0 Hz, 2H), 3.97 (t, J=5.7 Hz, 2H), 2.81 (t,J=5.7 Hz, 2H), 2.58 (s, 3H), 2.49 (m, 4H), 1.69 (m, 4H) ppm; MS (ES)408.5 (M+H), 406.5 (M−H).

In the following reaction schemes and examples, unless otherwise noted,reagents and solvents were used as received from commercial suppliers.Proton and carbon nuclear magnetic resonance spectra were obtained on aBruker AC 300 or a Bruker AV-300 spectrometer at 300 MHz for proton and75 MHz for carbon. Spectra are given in ppm (δ) and coupling constants,J, are reported in Hertz. Tetramethylsilane was used as an internalstandard for proton spectra and the solvent peak was used as thereference peak for carbon spectra. Infrared spectra were obtained on aNicolet Nexus 470 (ATR) spectrometer. Mass spectra were obtained on aPerkin Elmer Sciex 100 atmospheric pressure ionization (APCI) massspectrometer, or a Finnigan LCQ Duo LCMS ion trap electrosprayionization (ESI) mass spectrometer. Thin-layer chromatography (TLC) wasperformed using Analtech silica gel plates and visualized by ultraviolet(UV) light, iodine, or 20 wt % phosphomolybdic acid in ethanol. HPLCanalyses were obtained using a YMC J'Sphere ODS-M80 column (150×4.6 mm)with UV detection at 254 nm using a standard solvent gradient program(Method A). Elemental analyses were performed by QuantitativeTechnologies, Inc. (Whitehouse, N.J.).

Method 1: Time Flow (min) (mL/min) % A % B 0 1 90 10 15 1 0 100 25 1 0100 30 1 90 10 A = Water with 0.03 v/v Trifluoroacetic Acid B =Acetonitrile with 0.03 v/v Trifluoroacetic acid

Method 2: Time Flow (min) (mL/min) % A % B 0 1 90 10 15 1 0 100 25 1 0100 30 1 90 10 A = Water + 5% Acetonitrile (v/v) with 0.03 v/vTrifluoroacetic Acid B = Acetonitrile + 5% Water (v/v) with 0.03 v/vTrifluoroacetic Acid

Compounds (Ia-3), (Ia-4) and (Ia-5), as set forth below in ReactionScheme 1B, are compounds of formula (Ia), as set forth above in theSummary of the Invention, and are prepared as illustrated below inReaction Scheme 1B. For purposes of convenience, the minor products,i.e., the corresponding compounds of formula (Ib), are not illustratedin Reaction Scheme 1B, but it is understood that these compounds areprepared as well by the method disclosed therein and can be isolated andseparated from compounds (Ia-3), (Ia-4) and (Ia-5) by standard isolationand separation techniques.

In general, compound (Ia-3) was prepared by methods similar to thosedescribed in Reaction Scheme 1, Reaction Scheme 1A, and as describedbelow. Successful debenzylation of (Ia3) was accomplished by heating for5 days in cyclohexene in the presence of Pd/C. The alkylation of (Ia-4)with bromoacetonitrile gave (Ia-5).

Specifically, a mixture of 4-benzyloxyaniline hydrochloride 2b (10.26 g,43.5 mmol) and triethylamine (4.40 g, 43.5 mmol) in 2-propanol (100 mL)was stirred at ambient temperature. After 10 min,diphenylcyanocarbimidate 1 (10.37 g, 43.5 mmol) was added and stirringcontinued at ambient temperature. After 3.5 h the solids that formedwere collected by filtration, washing with 2-propanol, to afford 3b(14.64 g, 98%) as an off-white solid: ¹H NMR (300 MHz, DMSO-d₆) δ 10.68(br s, 1H), 7.47-7.02 (m, 14H), 5.11 (s, 2H).

A mixture of 3b (14.60 g, 42.5 mmol) and hydrazine hydrate (2.55 g, 51.0mmol) in MeOH (150 mL) was stirred at ambient temperature. After 2.25 h,additional hydrazine hydrate (1.28 g, 25.6 mmol) was added and stirringcontinued at ambient temperature for 1.5 h. The present solids werecollected by filtration, washing with 2-propanol, to afford 4b (8.0 g,67%) as a yellow solid: ¹H NMR (300 MHz, DMSO-d₆) δ 11.00 (br s, 1H),8.35 (br s, 1H), 7.43-7.24 (m, 7H), 6.83 (d, J=8.9 Hz, 2H), 5.78 (br s,2H), 5.01 (s, 2H).

To a stirred mixture of 4b (1.0 g, 3.57 mmol) and pyridine (0.28 g, 3.57mmol) in acetone (20 mL) at ice bath temperature was added p-toluoylchloride 7 (0.55 g, 3.57 mmol). After stirring for 1 h at ice bathtemperature and an additional 3 h at ambient temperature the reactionmixture was poured onto water (100 mL) and stirred vigorously. Thesolids that formed were collected by filtration and triturated with2-propanol (100 mL) to give 1.1 g of a yellow solid. Purification byflash chromatography (98:2 methylene chloride/methanol) afforded5-amino-3-[4-(benzyloxy)phenylamino]-1-(4-methylphenyl)carbonyl-1H-1,2,4-triazole(Ia-3) (0.72 g, 51%) as a yellow solid: ¹H NMR (300 MHz, DMSO-d₆) δ 9.10(br s, 1H), 8.13 (d, J=8.2 Hz, 2H), 7.78 (br s, 2H), 7.47-7.21 (m, 9H),6.92 (d, J=9.0 Hz, 2H), 5.03 (s, 2H), 2.42 (s, 3H).

A mixture of5-amino-3-[4-(benzyloxy)phenylamino]-1-(4-methylphenyl)carbonyl-1H-1,2,4-triazole(Ia-3) (3.95 g, 9.89 mmol) and 10% Pd/C (0.80 g) in cyclohexene (64 mL)and THF (128 mL) was stirred and heated at 70° C. After 2 d, additional10% Pd/C (0.80 g) was added and heating and stirring at 70° C. wascontinued for an additional 3 d. After cooling to ambient temperature,the mixture was filtered through diatomaceous earth and concentrated togive a yellow-brown residue. Purification by flash chromatography (95:5methylene chloride/methanol) followed by trituration with methylenechloride afforded5-amino-3-[4-(hydroxy)phenylamino]-1-(4-methylphenyl)carbonyl-1H-1,2,4-triazole(Ia-4) (1.08 g, 35%) as a pale yellow solid: R_(f) 0.36 (95:5 methylenechloride/methanol); mp 221-223° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 8.92 (s,1H), 8.88 (s, 1H), 8.13 (d, J=8.2 Hz, 2H), 7.74 (br s, 2H), 7.38-7.32(m, 4H), 6.64 (d, J=8.8 Hz, 2H), 2.42 (s, 3H); ¹³C NMR (75 MHz, DMSO-d₆)δ 166.1, 158.4, 157.3, 151.0, 142.9, 132.9, 130.6, 129.8, 128.4, 118.1,115.1, 21.1; IR (ATR) 1697 cm⁻¹; ESI MS m/z 310 [C₁₆H₁₆N₆O₂+H]⁺; HPLC(Method A) >99% (AUC), t_(R)=11.22 min. Anal. Calcd forC₁₆H₁₆N₆O₂.0.5H₂O: C, 60.47; H, 4.92; N, 22.04. Found: C, 60.27; H,4.70; N, 21.51.

A mixture of (Ia-4) (0.50 g, 1.62 mmol), potassium carbonate (0.25 g,1.78 mmol) and bromoacetonitrile (0.21 g, 1.78 mmol) in 2-butanone (5mL) was stirred at 75° C. After 18 h the reaction was cooled to ambienttemperature, diluted with ethyl acetate (100 mL), washed with water,brine, dried over magnesium sulfate and concentrated to afford 0.55 g ofa tan solid. Purification by flash chromatography (1:1 ethylacetate/hexanes), followed by recrystallization from acetonitrileafforded5-amino-3-[3-(cyanomethoxy)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole(Ia-5) (0.08 g, 14%) as a yellow solid: R_(f) 0.46 (95:5 methylenechloride/methanol); mp 236-241° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.23 (s,1H), 8.12 (d, J=8.0 Hz; 2H), 7.79 (br s, 2H), 7.50 (d, J=8.9 Hz, 2H),7.39 (d, J=8.0 Hz, 2H), 6.98 (d, J=8.9 Hz, 2H), 5.08 (s, 2H), 2.43 (s,3H); ¹³C NMR (75 MHz, DMSO-d₅) δ 166.6, 158.5, 157.7, 150.4, 143.3,136.5, 130.9, 130.1, 128.8, 118.0, 117.2, 115.9, 54.4, 21.5; IR (ATR)1687 cm⁻¹; APCI MS m/z 349 [C₁₈H₁₆N₆O₂+H]⁺; HPLC (Method A) 96.4% (AUC),t_(R)=13.31 min. Anal. Calcd for C₁₈H₁₆N₆O₂.0.25H₂O: C, 61.31; H, 4.65;N, 23.82. Found: C, 61.51; H, 4.41; N, 23.69.

Compounds (Ia-8) and (Ia-9), as set forth below in Reaction Scheme 1C,are compounds of formula (Ia), as set forth above in the Summary of theInvention, and are prepared as illustrated below in Reaction Scheme 10from compounds (Ia-6) and (Ia-7), which are both compounds of theinvention as well. The corresponding compounds of formula (Ib) of thesecompounds may be prepared in a similar manner.

In general, alkylation of compounds (Ia-6) and (Ia-7) with2-bromoacetonitrile in the presence of K₂CO₃ afforded compounds (Ia-8)and (Ia-9). Compounds (Ia-6) and (Ia-7) can be prepared according tomethods similar to those described above using the appropriatelysubstituted starting materials or by methods known to one skilled in theart.

In particular, to a solution of5-amino-3-[3-(hydroxy)phenylamino]-1-(2-(methyl)phenyl)carbonyl-1H-1,2,4-triazole(Ia-6) (0.23 g, 0.75 mmol) in 2-butanone (3 mL) was added K₂CO₃ (0.11 g,0.83 mmol) and BrCH₂CN (0.10 g, 0.83 mmol). After stirring the mixtureat 75° C. for 20 h, the 2-butanone was removed under reduced pressure.The residue was dissolved in EtOAc (50 mL), washed with water (50 mL),brine (30 mL), dried (Na₂SO₄) and concentrated to afford the crudeproduct. Purification by flash chromatography (1:1 hexanes/EtOAc) gave5-amino-3-[3-(cyanomethoxy)phenylamino]-1-(2-(methyl)phenyl)carbonyl-1H-1,2,4-triazole(Ia-8) (0.09 g, 35%) as a white solid: R_(f) 0.29 (1:1 hexanes/ethylacetate); mp (DSC) 204.5-207.9° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.43 (s,1H), 7.84 (s, 2H), 7.56 (d, J=7.6 Hz, 1H), 7.46-7.41 (m, 1H), 7.35-7.22(m, 3H), 7.11 (t, J=8.1 Hz, 1H), 6.96-6.93 (m, 1H), 6.48 (dd, J=8.0, 2.2Hz, 1H), 4.80 (s, 2H), 2.31 (s, 3H); ¹³C NMR (75 MHz, DMSO-d₆) δ 168.8,158.5, 157.0, 156.9, 142.7, 135.5, 134.7, 130.5, 130.4, 129.8, 128.1,125.5, 116.7, 111.2, 106.3, 103.3, 53.3, 19.5; IR (ATR) 3448, 3368,2325, 1689 cm⁻¹; APCI MS m/z 349 [C₁₈H₁₆N₆O₂+H]⁺; HPLC (Method A) 91.3%(AUC), t_(R)=12.46 min.

Alternatively, to a solution of5-amino-3-[3-(hydroxy)phenylamino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole(Ia-7) (0.84 g, 2.7 mmol) in 2-butanone (9 mL) was added K₂CO₃ (0.41 g,3.0 mmol) and BrCH₂CN (0.36 g, 3.0 mmol). After stirring the mixture at75° C. for 20 h, the 2-butanone was removed under reduced pressure. Theresidue was dissolved in EtOAc (50 mL), washed with water (50 mL), brine(30 mL), dried (Na₂SO₄) and concentrated to afford the crude product.Recrystallization from CH₃CN afforded5-amino-3-[3-(cyanomethoxy)phenylamino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole(Ia-9) (0.12 g, 13%) as a white solid: R_(f) 0.22 (1:1 hexanes/ethylacetate); mp (DSC) 220.0-224.4° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.45 (s,1H), 8.05 (s, 1H), 7.91 (d, J=7.1 Hz, 1H), 7.83 (s, 2H), 7.50-7.39 (m,3H), 7.20 (t, J=8.1 Hz, 1H), 7.12-7.09 (m, 1H), 6.56 (dd, J=7.9, 2.2 Hz,1H), 5.04 (s, 2H), 2.43 (s, 3H); ¹³C NMR (75 MHz, DMSO-d₆) δ 166.6,157.9, 157.2, 156.9, 142.3, 137.2, 133.0, 132.6, 130.8, 129.5, 127.8,127.4, 116.5, 111.1, 105.2, 104.0, 53.3, 20.8; IR (ATR) 3449, 3367,2325, 1684 cm⁻¹; APCI MS m/z 349 [C₁₈H₁₆N₆O₂+H]⁺; HPLC (Method A) 96.8%(AUC), t_(R)=12.81 min.

Compounds (Ia-10) and (Ia-11), as set forth below in Reaction Scheme 1D,are compounds of formula (Ia), as set forth above in the Summary of theInvention, and are prepared as illustrated below in Reaction Scheme 1D.For purposes of convenience, the minor products, i.e., the correspondingcompounds of formula (Ib), are not illustrated in Reaction Scheme 1D,but it is understood that these compounds are prepared as well by themethod disclosed therein and can be isolated and separated fromcompounds (Ia-10) and (Ia-11) by standard isolation and separationtechniques.

In general, compound (Ia-11) is prepared by the acylation of compound 4bwith the compound 8, followed by removal of the benzyl group. Compound4b can be prepared by methods similar to those described herein or bymethods known to one skilled in the art.

Specifically, to a stirred mixture of 4-isopropoxy benzoic acid (10.0 g,55.5 mmol) and DMF (1 drop) in methylene chloride (80 mL) was addeddropwise over a period of 15 min, a solution of oxalyl chloride (7.40 g,58.2 mmol) in methylene chloride (20 mL). After stirring for 2.45 h atambient temperature the reaction mixture was concentrated, taken up intoa small amount of methylene chloride, filtered to remove insolubles andagain concentrated to afford 8 (10.38 g, 94%) as a yellow liquid: ¹H NMR(300 MHz, CDCl₃) δ 8.05 (d, 2H), 6.94 (d, 2H), 4.68 (m, 1H), 1.44 (d,6H).

To a stirred mixture of 8 (0.50 g, 1.78 mmol) and pyridine (0.14 g, 1.78mmol) in acetone (15 mL) at ice bath temperature was added 31 (0.35 g,1.78 mmol). After stirring for 1 h at ice bath temperature and anadditional 21.5 h at ambient temperature the reaction mixture was pouredonto water (150 mL) and stirred vigorously. The aqueous mixture wasextracted with ethyl acetate and the organic layer was separated, washedwith brine, dried over magnesium sulfate and concentrated to give 0.74 gof a yellow foam. Purification by flash chromatography (97:3 methylenechloride/methanol) afforded5-amino-3-[4-(benzyloxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole(Ia-10) (0.52 g, 51%) as a yellow solid: R_(f) 0.51 (95:5 methylenechloride/methanol); mp 79-81° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.08 (s,1H), 8.26 (d, J=8.9 Hz, 2H), 7.75 (br s, 2H), 7.60-7.20 (m, 7H), 7.08(d, J=9.0 Hz, 2H), 6.93 (d, J=9.0 Hz, 2H), 5.26 (s, 2H), 4.80 (m, 1H),1.33 (d, J=6.0 Hz, 6H); ¹³C NMR (75 MHz, DMSO-d₆) δ 165.8, 161.4, 158.6,157.8, 152.5, 137.7, 135.1, 133.5, 128.7, 128.0, 127.9, 124.4, 118.1,115.4, 114.8, 69.9, 69.8, 22.0; IR (ATR) 1669, 1581, 1544, 1506 cm⁻¹;ESI MS m/z 444 [C₂₅H₂₅N₅O₃+H]⁺; HPLC (Method A)>99% (AUC), t_(R)=16.27min. Anal. Calcd for C₂₅H₂₅N₅O₃: C, 67.70; H, 5.68; N, 15.79. Found: C,67.73; H, 5.63; N, 15.79.

A mixture of (Ia-10) (0.36 g, 0.812 mmol) and 10% Pd/C (0.072 g) incyclohexene (6 mL) and THF (12 mL) was stirred and heated at 70° C.After 2 d, additional 10% Pd/C (0.036 g) was added and heating andstirring at 70° C. was continued for an additional 3 d. After cooling toambient temperature, the mixture was filtered through diatomaceous earthand concentrated to give a yellow-brown residue. Purification by flashchromatography (95:5 methylene chloride/methanol) afforded5-amino-3-[4-(hydroxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole(Ia-11) (0.14 g, 48%) as a tan solid: R_(f) 0.37 (95:5 methylenechloride/methanol); mp 229-234° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 8.91 (s,1H), 8.88 (s, 1H), 8.26 (d, J=8.9 Hz, 2H), 7.72 (br s, 2H), 7.34 (d,J=8.8 Hz, 2H), 7.07 (d, J=8.9 Hz, 2H), 6.65 (d, J=8.8 Hz, 2H), 4.79 (m,1H), 1.32 (d, J=6.0 Hz, 6H); ¹³C NMR (75 MHz, DMSO-d₆) δ 165.8, 161.4,158.7, 157.8, 151.4, 133.5, 133.4, 124.4, 118.5, 115.5, 114.8, 70.0,55.3, 22.0; IR (ATR) 1652, 1607, 1573, 1505 cm⁻¹; ESI MS m/z 354[C₁₈H₁₃N₅O₃+H]⁺; HPLC (Method A)>99% (AUC), t_(R)=11.74 min. Anal. Calcdfor C₁₈H₁₉N₅O₃.0.5H₂O: C, 59.74; H, 5.43; N, 19.32. Found: C, 59.94; H,5.08; N, 19.00.

Compound (Ia-12), as set forth below in Reaction Scheme 1E, is acompound of formula (Ia), as set forth above in the Summary of theInvention, and is prepared as illustrated below in Reaction Scheme 1E.For purposes of convenience, the minor product, i.e., the correspondingcompound of formula (Ib), is not illustrated in Reaction Scheme 1E, butit is understood that this compound is prepared as well by the methoddisclosed therein and can be isolated and separated from compound(Ia-12) by standard isolation and separation techniques.

In general, compound (Ia-12) was prepared as shown above in ReactionScheme 1E from commercially available 4-nitrophenol 9.

Specifically, a mixture of 4-nitrophenol 9 (6.00 g, 43.1 mmol),bromoacetonitrile (5.05 g, 47.4 mmol) and potassium carbonate (6.56 g,47.4 mmol) in acetonitrile (120 mL) was heated to 50° C. for 5 h. Thereaction was concentrated to remove most of the acetonitrile, extractedwith ethyl acetate (25 mL), washed with water (25 mL), 1 N aqueoussodium hydroxide (25 mL), brine, dried (MgSO₄) and concentrated toafford 10 (7.49 g, 97%) as a tan-yellow solid: ¹H NMR (300 MHz, DMSO-d₆)δ 8.29 (dd, J=2.1, 7.2 Hz, 2H), 7.29 (dd, J=7.2, 2.1 Hz, 2H), 5.36 (s,2H).

A mixture of 10 (5.42 g, 30.4 mmol), sodium dithionite (15.89 g, 91.2mmol) and sodium bicarbonate (15.30 g, 182.0 mmol) in 1:2 ethanol/water(75 mL) was stirred at ambient temperature for 20 h. Water (25 mL) wasadded and the pH of the resultant solution was adjusted to pH 10 with 1N aqueous sodium hydroxide. The aqueous solution was extracted withmethylene chloride (3×200 mL), the combined organic layers wereseparated, dried (MgSO₄) and concentrated to afford crude product 2c(0.73 g, 16%) as a yellow oil: ¹H NMR (300 MHz, DMSO-d₆) δ 6.78 (dd,J=7.5, 3.0 Hz, 2H), 6.55 (dd, J=7.5, 3.0 Hz, 2H), 4.96 (s, 2H), 4.83 (brs, 2H).

A mixture of 2c (0.86 g, 5.79 mmol) and diphenylcyanocarbimidate 1 (1.38g, 5.79 mmol) in 2-propanol (20 mL) was stirred at ambient temperaturefor 17 h. The solids that formed were collected by filtration and washedwith 2-propanol, to afford 3c (0.99 g, 58%) as an off-white solid: ¹HNMR (300 MHz, CDCl₃) δ 8.90 (br s, 1H), 7.44-7.33 (m, 5H), 7.52 (d,J=7.9 Hz, 2H), 7.12 (dd, J=3.0, 7.9 Hz, 2H), 4.77 (s, 2H); ESI MS m/z293 [C₁₆H₁₂N₄O₂+H]⁺.

A mixture of 3c (0.99 g, 3.38 mmol) and hydrazine hydrate (0.16 g, 3.38mmol) in 2-propanol (20 mL) was stirred at ambient temperature for 24 h.The solids that formed were collected by filtration and washed with2-propanol, to afford 4c (0.58 g, 74%) as an off-white solid: ¹H NMR(300 MHz, DMSO-d₆) δ 11.09 (s, 1H), 8.53 (s, 1H), 7.48 (dd, J=3.0, 9.0Hz, 2H), 6.91 (dd, J=3.0, 9.0 Hz, 2H), 5.83 (br s, 2H), 5.04 (s, 2H);ESI MS m/z 231 [C₁₀H₁₀N₆O+H]⁺.

To a stirred ice-cold mixture of 4c (0.50 g, 2.17 mmol) and pyridine(0.17 g, 2.17 mmol) in acetone (35 mL) was added 4-isopropoxybenzoylchloride 8 (0.43 g, 2.17 mmol). After stirring for 1 h at ice bathtemperature and an additional 16 h at ambient temperature, the reactionmixture was slowly added to a vigorously stirred solution of water (100mL). The crude product formed a yellow precipitate, which was collectedby filtration. Purification by flash chromatography (98:2 methylenechloride/methanol) afforded5-amino-3-[4-(cyanomethoxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole(Ia-12) (0.27 g, 31%) as a beige solid: R_(f) 0.72 (97:3 methylenechloride/methanol); mp (DSC) 182.9-186.1° C.; ¹H NMR (300 MHz, DMSO-d₆)δ 9.22 (s, 1H), 8.25 (d, J=9.0 Hz, 2H), 7.77 (br s, 2H), 7.52 (d, J=9.0Hz, 2H), 7.09 (d, J=9.0 Hz, 2H), 7.00 (d, J=9.0 Hz, 2H), 5.09 (s, 2H),4.94-4.78 (m, 1H), 1.33 (d, J=6.0 Hz, 6H); ¹³C NMR (75 MHz, DMSO-d₆)165.5, 161.0, 158.1, 157.4, 150.0, 136.2, 133.0, 123.9, 117.7, 116.7,115.5, 114.4, 69.5, 54.0, 21.6; IR (ATR) 3353, 3098, 1678, 1585, 1506cm⁻¹; ESI MS m/z 393 [C₂₀H₂₀N₆O₃+H]⁺; HPLC (Method A) 94.3% (AUC),t_(R)=14.00 min.

Compound (Ia-13), as set forth below in Reaction Scheme 1F, is acompound of formula (Ia), as set forth above in the Summary of theInvention, and is prepared as illustrated below in Reaction Scheme 1F.For purposes of convenience, the minor product, i.e., the correspondingcompound of formula (Ib), is not illustrated in Reaction Scheme 1F, butit is understood that this compound is prepared as well by the methoddisclosed therein and can be isolated and separated from compound(Ia-13) by standard isolation and separation techniques.

In general, compound (Ia-13) is prepared as shown above in ReactionScheme 1F starting from commercially available 3-nitrophenol 11.

Specifically, to a solution of 3-nitrophenol 11 (2.00 g, 14.4 mmol) in1,4-dioxane (40 mL) was added tetrahydro-2H-pyran (4.84 g, 57.5 mmol)and p-TsOH (a few crystals). The reaction mixture was stirred at ambienttemperature under N₂ for 60 h. The dioxane was removed under reducedpressure and the crude oil obtained was diluted with EtOAc (100 mL). Theorganic layer was washed with 1 N NaOH (2×50 mL), brine (30 mL), dried(Na₂SO₄) and concentrated to afford 12 (3.08 g, 96%) as a yellow oil: ¹HNMR (300 MHz, CDCl₃) δ 7.92-7.90 (m, 1H), 7.86-7.82 (m, 1H), 7.45-7.34(m, 2H), 5.50 (t, J=2.7 Hz, 1H), 3.89-3.81 (m, 1H), 3.68-3.61 (m, 1H),2.01-1.95 (m, 1H), 1.92-1.87 (m, 2H), 1.75-1.58 (m, 3H).

A mixture of 12 (3.08 g, 13.8 mmol) and 10% Pd/C (0.30 g) in EtOH (150mL) at ambient temperature was shaken in an atmosphere of hydrogen at 50psi. After 1 h, the reaction mixture was filtered through diatomacconsearth and the solids washed with EtOH. The filtrate was concentrated toafford 2d (2.62 g, 98%) as a yellow oil: ¹H NMR (300 MHz, CDCl₃) δ 7.04(t, J=8.0 Hz, 1H), 6.47-6.41 (m, 2H), 6.34-6.30 (m, 1H), 5.37 (t, J=3.2Hz, 1H), 3.95-3.87 (m, 1H), 3.72-3.56 (m, 3H), 2.02-1.89 (m, 1H),1.85-1.80 (m, 2H), 1.75-1.54 (m, 3H).

A mixture of 2d (2.62 g, 13.6 mmol) and diphenylcyanocarbimidate (3.23g, 13.6 mmol) in 2-PrOH (40 mL) was stirred at ambient temperature underN₂ for 20 h. The solids that formed were collected by filtration andwashed with 2-PrOH to afford 3d (3.08 g, 67%) as a white solid: ¹H NMR(300 MHz, CDCl₃) δ 7.90 (br s, 1H), 7.47-7.40 (m, 2H), 7.36-7.28 (m,2H), 7.21-7.14 (m, 2H), 7.10 (t, J=2.1 Hz, 1H), 6.97 (dt, J=7.6, 1.6 Hz,2H), 5.40 (t, J=3.2 Hz, 1H), 3.87 (dt, J=11.7, 3.0 Hz, 1H), 3.63-3.58(m, 1H), 2.05-1.91 (m, 1H), 1.88-1.83 (m, 2H), 1.74-1.62 (m, 3H).

A mixture of 3d (3.08 g, 9.16 mmol) and hydrazine monohydrate (0.46 g,9.16 mmol) in MeOH (40 mL) was stirred at ambient temperature for 20 h.The MeOH was removed under reduced pressure and the crude oil obtainedwas partitioned between EtOAc (100 mL) and water (100 mL). The aqueouslayer was extracted with EtOAc (100 mL) and the combined organicextracts were washed with brine (30 mL), dried (Na₂SO₄) and concentratedto give the crude product. Purification by flash chromatography (CH₂Cl₂then 9:1 CH₂Cl₂/MeOH) afforded 4d (1.81 g, 72%) as a white foam: ¹H NMR(300 MHz, DMSO-d₆) δ 11.12 (s, 1H), 8.58 (s, 1H), 7.38 (s, 1H),7.03-7.01 (m, 2H), 6.42-6.38 (m, 1H), 5.86 (s, 2H), 5.35 (t, J=3.0 Hz,1H), 3.81-3.73 (m, 1H), 3.55-3.48 (m, 1H), 1.88-1.53 (m, 6H).

To a ice-cold mixture of 4d (0.50 g, 1.80 mmol) and pyridine (0.14 g,1.80 mmol) in acetone (25 mL) was added dropwise a solution of4-isopropoxybenzoyl chloride (8) (0.36 g, 1.80 mmol) in acetone (5 mL)over 2 min and the resulting solution was stirred at ambient temperaturefor 20 h. The acetone was removed under reduced pressure and the crudeyellow foam obtained was dissolved in MeOH and p-TsOH (a few crystals)was added. After stirring for 7 d at ambient temperature, the MeOH wasremoved under reduced pressure and the residue partitioned between EtOAc(100 mL) and water (100 mL). The organic layer was washed with brine (30mL), dried (Na₂SO₄), and concentrated to give the crude product.Purification by flash chromatography (95:5 CH₂Cl₂/MeOH) gave5-amino-3-[3-(hydroxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole(Ia-13) (0.22 g, 35%) as a yellow solid: R_(f) 0.53 (9:1 CH₂Cl₂/MeOH);mp (DSC) 204.2-211.9° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.17 (s, 1H), 9.13(s, 1H), 8.26 (d, J=8.8 Hz, 2H), 7.75 (s, 2H), 7.07-6.96 (m, 5H),6.29-6.26 (m, 1H), 4.82-4.74 (m, 1H), 1.32 (d, J=5.9 Hz, 6H); ¹³C NMR(75 MHz, DMSO-d₆) δ 165.9, 161.4, 158.4, 158.0, 157.7, 142.4, 133.5,129.6, 124.3, 114.8, 108.2, 107.8, 104.4, 70.0, 22.0; IR (ATR) 3426,3305, 1661 cm⁻¹; APCI MS m/z 354 [C₁₈H₁₉N₆O₃+H]⁺; HPLC (Method A) >99%(AUC), t_(R)=12.24 min. Anal. Calcd for C₁₆H₁₉N₆O₃: C, 61.18; H, 5.42;N, 19.82. Found: C, 61.10; H, 5.29; N, 19.69.

Compounds (Ia-14) and (Ia-15), as set forth below in Reaction Scheme 1G,are compounds of formula (Ia), as set forth above in the Summary of theInvention, and are prepared as illustrated below in Reaction Scheme 1G.For purposes of convenience, the minor products, i.e., the correspondingcompounds of formula (Ib), are not illustrated in Reaction Scheme 1G,but it is understood that these compounds are prepared as well by themethod disclosed therein and can be isolated and separated fromcompounds (Ia-14) and (Ia-15) by standard isolation and separationtechniques.

In general, condensation of benzyloxyaniline anddiphenylcyanocarbonimidate afforded intermediate 3e, which was thentreated with hydrazine to give triazole 4e. Acylation of 4e withp-toluoyl chloride (13) in the presence of pyridine afforded compound(Ia-14) in good yield. Initial attempts to remove the benzyl protectinggroup by hydrogenolysis with Pd/C (50 psi) were unsuccessful.Deprotection of compound (Ia-14) was achieved with cyclohexene in thepresence of 10% Pd/C and refluxing THF to provide (Ia-15).

Specifically, a solution of 3-benzyloxyaniline 2e (0.84 g, 4.2 mmol) anddiphenylcyanocarbonimidate 1 (1.0 g, 4.2 mmol) in 2-PrOH (15 mL) wasstirred at ambient temperature under N₂. After 5 h, the solids werecollected by filtration washing with cold 2-PrOH to afford 3e (1.25 g,86%) as a white solid: ¹H NMR (300 MHz, DMSO-d₆) δ 7.47-7.26 (m, 12H),7.17 (s, 1H), 7.05 (d, J=7.9 Hz, 1H), 6.90 (d, J=8.3 Hz, 1H), 5.10 (s,2H).

To a mixture of 3e (1.25 g, 3.6 mmol) in CH₃OH (20 mL) was addedNH₂NH₂.H₂O (0.2 g, 3.8 mmol) dropwise. Once the addition was completed,the reaction was stirred at ambient temperature. After 2 h, the methanolwas removed under reduced pressure and the residue partitioned betweenwater (50 mL) and EtOAc (50 mL). The organic layer was washed with brine(20 mL), dried (Na₂SO₄), filtered, and concentrated. The crude foamobtained was purified by flash chromatography (9:1 CH₂Cl₂/CH₃OH) toafford 4e (0.93 g, 93%) as a white solid: ¹H NMR (300 MHz, DMSO-d₆) δ11.13 (s, 1H), 8.61 (s, 1H), 7.46-7.32 (m, 6H), 7.04-6.97 (m, 2H), 6.37(d, J=7.1 Hz, 1H), 5.86 (s, 2H), 5.02 (s, 2H).

Pyridine (0.56 g, 7.1 mmol) was added to a mixture of 4e (2.0 g, 7.1mmol) and acetone (60 mL) at ambient temperature under N₂. The reactionwas cooled to 0° C. and p-toluoyl chloride (1.1 g, 7.1 mmol) was addeddropwise over 2 min. Once the addition was complete, the reaction wasstirred at ambient temperature for 1 h. The acetone was removed underreduced pressure and the residue diluted in water (150 mL). Solids werecollected by filtration, washing with water, and then purified by flashchromatography (95:5 CH₂Cl₂/CH₃OH) to afford5-amino-3-[3-(benzyloxy)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole(Ia-14) (2.12 g, 75%) as a pale-yellow solid: ¹H NMR (300 MHz, DMSO-d₆)δ 9.35 (s, 1H), 8.10 (d, J=8.1 Hz, 2H), 7.79 (br s, 2H), 7.59 (t, J=2.1Hz, 1H), 7.41-7.34 (m, 5H), 7.27 (d, J=8.1 Hz, 2H), 7.11 (t, J=8.1 Hz,1H), 6.89 (dd, J=1.3, 8.0 Hz, 1H), 6.47 (dd, J=2.3, 7.9 Hz, 1H), 4.91(s, 2H), 2.20 (s, 3H).

To a solution of5-amino-3-[3-(benzyloxy)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole(Ia-14) (0.50 g, 1.3 mmol) in THF (20 mL) was added cyclohexene (10 mL)and 10% Pd/C (0.10 g). The reaction was stirred at 90° C. under N₂ for48 h, then filtered through diatomaceous earth, washing with THF, andconcentrated to give a yellow-orange solid. Purification by flashchromatography (95:5 CH₂Cl₂/CH₃OH) followed by triturated in CH₂Cl₂afforded5-amino-3-[3-(hydroxy)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole(Ia-15) (0.05 g, 14%) as a yellow solid: R_(f) 0.22 (95:5 CH₂Cl₂/CH₃OH);mp (DSC) 2 endothermic events, 214.7-217.5° C., 322.1-329.8° C., 1exothermic event, 226.8-228.8° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.14 (d,J=8.1 Hz, 2H), 8.13 (d, J=8.2 Hz, 2H), 7.77 (s, 2H), 7.36 (d, J=8.1 Hz,2H), 6.99-6.94 (m, 3H), 6.29-6.25 (m, 1H), 2.45 (s, 3H); ¹³C NMR (75MHz, DMSO-d₆) δ 166.2, 158.2, 157.6, 157.3, 142.9, 142.0, 130.6, 129.7,129.1, 128.5, 107.8, 107.4, 104.0, 21.0; IR (ATR) 3363, 1668 cm⁻¹; APCIMS m/z 310 [C₁₆H₁₅N₅O₂+H]⁺; HPLC (Method A) 96.9% (AUC), t_(R)=11.5 min.Anal. Calcd for C₁₆H₁₆N₆O₂.0.50H₂O: C, 60.47; H, 4.92; N, 22.03. Found:C, 60.87; H, 4.65; N, 21.75.

Compounds (Ia-16) and (Ia-17), as set forth below in Reaction Scheme 1H,are compounds of formula (Ia), as set forth above in the Summary of theInvention, and are prepared as illustrated below in Reaction Scheme 1H.For purposes of convenience, the minor products, i.e., the correspondingcompounds of formula (Ib), are not illustrated in Reaction Scheme 1H,but it is understood that these compounds are prepared as well by themethod disclosed therein and can be isolated and separated fromcompounds (Ia-16) and (Ia-17) by standard isolation and separationtechniques.

In general, compounds of (Ia-16) and (Ia-17) are prepared from theacylation of compounds 4d and 4e, respectively, with compound 14.Compounds 4d and 4e can be prepared by methods disclosed herein or bymethods known to one skilled in the art.

Specifically, to an ice-cold mixture of 4d (0.50 g, 1.80 mmol) andpyridine (0.28 g, 3.60 mmol) in acetone (10 mL) placed under N₂ wasadded dropwise a solution of 3-isopropoxybenzoyl chloride 14 (0.36 g,1.80 mmol) in acetone (5 mL) over 2 min and the resulting solution wasstirred at ambient temperature for 20 h. The acetone was concentrated toa small volume (5 mL) and diluted in water (15 mL). The resultingprecipitate was collected by filtration, dissolved in acetone and theorganic solution dried (Na₂SO₄) and concentrated to afford a yellowfoam. The yellow foam and p-TsOH (a few crystals) in MeOH (15 mL) wasstirred at 50° C. for 24 h then at ambient temperature for 6 d. The MeOHwas removed under reduced pressure and the residue was partitionedbetween EtOAc (30 mL) and water (30 mL). The aqueous layer was extractedwith EtOAc (20 mL) and the combined organics were dried (Na₂SO₄), andconcentrated to give the crude product. Purification by flashchromatography (95:5 CH₂Cl₂/MeOH) followed by trituration with CH₂Cl₂afforded5-amino-3-[3-(hydroxy)phenylamino]-1-(3-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole(Ia-16) (0.36 g, 38%) as a yellow solid: R_(f) 0.55 (9:1 CH₂Cl₂/MeOH);mp (DSC) 211.3-214.8° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.16 (d, J=3.1 Hz,2H), 7.80-7.74 (m, 3H), 7.67 (d, J=7.7 Hz, 1H), 7.44 (t, J=8.0 Hz, 1H),7.19 (dd, J=8.0, 2.2 Hz, 1H), 7.04-6.89 (m, 3H), 6.27 (dd, J=7.8, 1.4Hz, 1H), 4.72-4.64 (m, 1H), 1.29 (d, J=6.0 Hz, 6H); ¹³C NMR (75 MHz,DMSO-d₆) δ 166.5, 158.6, 158.0, 157.7, 157.1, 142.3, 134.2, 129.5,129.4, 122.7, 120.5, 117.5, 108.1, 107.9, 104.4, 70.0, 22.1; IR (ATR)3424, 3365, 1689 cm⁻¹; APCI MS m/z 354 [C₁₈H₁₉N₅O₃+H]⁺; HPLC (Method A)97.9% (AUC), t_(R)=12.10 min. Anal. Calcd for C₁₅H₁₃N₅O₃: C, 61.18; H,5.42; N, 19.82. Found: C, 61.11; H, 5.33; N, 19.68.

Alternatively, to an ice cold mixture of 4e (0.30 g, 1.07 mmol) andpyridine (0.08 g, 1.07 mmol) in acetone (25 mL) under N₂ was addeddropwise a solution of 3-isopropoxybenzoyl chloride 14 (0.21 g, 1.07mmol) in acetone (5 mL) over 2 min and the resulting solution wasstirred at ambient temperature for 20 h. The acetone was concentrated toa small volume (5 mL) and diluted in water (15 mL). The resultingprecipitate was collected by filtration, dissolved in acetone and theorganic solution dried (Na₂SO₄) and concentrated to afford5-amino-3-[3-(benzyloxy)phenylamino]-1-(3-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole(Ia-17) (0.10 g, 21%) as a yellow solid: R_(f) 0.63 (9:1 CH₂Cl₂/MeOH);mp (DSC) 131.1-132.4° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.31 (s, 1H), 7.80(s, 2H), 7.70-7.63 (m, 2H), 7.40-7.31 (m, 7H), 7.14-7.01 (m, 3H),6.48-6.47 (m, 1H), 4.92 (s, 2H), 4.66-4.58 (m, 1H), 1.24 (d, J=6.0 Hz,6H); ¹³C NMR (75 MHz, DMSO-d₆) δ 165.1, 157.5, 156.8, 155.9, 155.5,140.8, 135.7, 132.9, 127.9, 127.7, 127.0, 126.4, 126.2, 120.9, 118.4,115.7, 108.1, 105.3, 101.9, 68.3, 67.5, 20.4; IR (ATR) 3685, 3434, 3343,1674 cm⁻¹; APCI MS m/z 444 [C₂₅H₂₅N₅O₃+H]⁺; HPLC (Method A)>99% (AUC),t_(R)=16.29 min. Anal. Calcd for C₂₅H₂₅N₅O₃.0.25H₂O: C, 66.70; H, 5.68;N, 15.79. Found: C, 67.42; H, 5.71; N, 15.63.

Compounds 2f, 2g and 2h, as set forth below in Reaction Scheme 1I, areintermediates in the preparation of compounds of the invention and areprepared as illustrated below in Reaction Scheme 1I. In Scheme 1I, “X”represents, e.g., an appropriate leaving group on the R as represented.Typical leaving groups include halides, such as bromide, chloride,iodide and the like.

Specifically, a mixture of 3-nitrophenol 11 (2.0 g, 14.3 mmol), K₂CO₃(4.17 g, 30.2 mmol), and N-(2-chloroethyl)morpholine hydrochloride (2.94g, 15.8 mmol) in DMF (20 mL) was stirred under N₂ at 50° C. for 5 h. TheDMF was removed under reduced pressure and the residue was partitionedbetween EtOAc (50 mL) and water (50 mL). The aqueous layer was extractedwith EtOAc (50 mL) and the combined organics were dried (Na₂SO₄) andconcentrated to give 15a (3.39 g, 94%) as a brown oil: ¹H NMR (300 MHz,CDCl₃) δ 7.85-7.81 (m, 1H), 7.76-7.74 (m, 1H), 7.45-7.40 (m, 1H),7.25-7.24 (m, 1H), 4.18 (t, J=5.5 Hz, 2H), 3.76-3.71 (m, 4H), 2.84 (t,J=5.5 Hz, 2H), 2.61-2.50 (m, 4H).

A mixture of 15a (3.39 g, 13.4 mmol) and 10% Pd/C (0.17 g) in EtOH (100mL) at ambient temperature was shaken in an atmosphere of hydrogen at 50psi. After 1 h, the reaction was filtered through diatomaceous earth,the solids washed with EtOAc and the filtrate concentrated to give thecrude product. Purification by flash chromatography (95:5 CH₂Cl₂/MeOH)afforded 2f (1.68 g, 56%) as a brown oil: ¹H NMR (300 MHz, CDCl₃) δ 7.04(t, J=8.0 Hz, 1H), 6.33-6.24 (m, 3H), 4.07 (t, J=5.7 Hz, 2H), 3.75-3.72(m, 4H), 3.65 (s, 2H), 2.78 (t, J=5.7 Hz, 2H), 2.59-2.56 (m, 4H).

Alternatively, a mixture of 3-nitrophenol 11 (3.0 g, 21.6 mmol), K₂CO₃(6.56 g, 47.4 mmol), and 1-(2-chloroethyl)piperidine hydrochloride (4.80g, 25.9 mmol) in DMF (30 mL) was stirred at 50° C. under N₂ for 48 h.The DMF was removed under reduced pressure and the residue waspartitioned between EtOAc (100 mL) and water (100 mL). The organic layerwas washed with water (2×50 mL), dried (Na₂SO₄) and concentrated to givethe crude product. Purification by flash chromatography (95:5CH₂Cl₂/MeOH) gave 15b (2.90 g, 54%) as a brown oil: ESI MS m/z 251[C₁₃H₁₈N₂O₃+H]⁺.

A mixture of 15b (2.90 g, 11.6 mmol) and 10% Pd/C (0.22 g) in EtOH (150mL) at ambient temperature was shaken in an atmosphere of hydrogen at 50psi. After 30 min, the reaction was filtered through diatomaceous earth,the solids washed with EtOAc and the filtrate was concentrated to afford2g (2.57 g, quantitative) as a brown oil: ¹H NMR (300 MHz, CDCl₃) δ 6.86(t, J=8.3 Hz, 1H), 6.13-6.11 (m, 2H), 6.07-6.04 (m, 1H), 5.01 (s, 2H),3.92 (t, J=6.0 Hz, 2H), 2.95 (t, J=6.0 Hz, 2H), 2.40-2.38 (m, 4H),1.52-1.36 (m, 6H).

Alternatively, a mixture of 3-nitrophenol 11 (3.0 g, 21.6 mmol), K₂CO₃(3.40 g, 24.8 mmol), and 2-(2-bromoethyl)-1,3-dioxolane (4.49 g, 24.8mmol) in CH₃CN (30 mL) was stirred under N₂ at 50° C. for 24 h. TheCH₃CN was removed under reduced pressure and the residue was partitionedbetween EtOAc (75 mL) and water (75 mL). The aqueous layer was extractedwith EtOAc (75 mL) and the combined organic extracts were washed with 1N NaOH (2×30 mL), water (30 mL), dried (Na₂SO₄), and concentrated toafford 15c (5.11 g, 99%) as a yellow oil: ¹H NMR (300 MHz, DMSO-d₆) δ7.83-7.80 (m, 1H), 7.71-7.69 (m, 1H), 7.58 (t, J=8.2 Hz, 1H), 7.44-7.40(m, 1H), 5.00 (t, J=4.9 Hz, 1H), 4.20 (t, J=6.5 Hz, 2H), 3.95-3.76 (m,4H), 2.13-2.03 (m, 2H).

A mixture of 15c (5.11 g, 21.4 mmol) and 10% Pd/C (0.30 g) in EtOH (175mL) at ambient temperature was shaken in an atmosphere of hydrogen at 50psi. After 30 min, the reaction was filtered through diatomaceous earth,the solids washed with EtOAc and the filtrate was concentrated to afford2h (4.51 g, quantitative) as a brown oil: ESI MS m/z 210 [C₁₁H₁₅NO₃+H]⁺.

Compounds (Ia-18) and (Ia-19), as set forth below in Reaction Scheme 1J,are compounds of formula (Ia), as set forth above in the Summary of theInvention, and are prepared as illustrated below in Reaction Scheme 1J.For purposes of convenience, the minor products, i.e., the correspondingcompounds of formula (Ib), are not illustrated in Reaction Scheme 1J,but it is understood that these compounds are prepared as well by themethod disclosed therein and can be isolated and separated fromcompounds (Ia-18) and (Ia-19) by standard isolation and separationtechniques.

In general, alkylation of 3-nitrophenol 11 was performed using reagentsRX which are commercially available or prepared by methods disclosedherein to afford intermediates (Ia-18) and (Ia-19). In Reaction Scheme1J, “X” represents, e.g., an appropriate leaving group on the R asrepresented. Typical leaving groups include halides, such as bromide,chloride, iodide and the like.

Specifically, the alkylation of 3-nitrophenol 11 was performed asdescribed above in Reaction Scheme 1I using 18, prepared as describedbelow in Reaction Scheme 1K, to afford 16a (3.02 g, 34%) as ayellow-orange solid: ¹H NMR (300 MHz, DMSO-d₆) δ 8.14-8.10 (m, 1H),7.87-7.83 (m, 1H), 7.76 (t, J=2.3 Hz, 1H), 7.60 (t, J=8.2 Hz, 1H),7.46-7.42 (m, 1H), 4.64 (s, 2H), 3.53 (t, J=4.6 Hz, 4H), 3.26 (q, J=6.6Hz, 2H), 2.38-2.33 (m, 6H).

The reduction of 16a was performed as described above in Reaction Schemeto afford 21 (2.81 g, quantitative) as a yellow oil: ¹H NMR (300 MHz,DMSO-d₆) δ 7.83-7.79 (m, 1H), 6.89 (t, J=7.9 Hz, 1H), 6.19-6.06 (m, 3H),5.10 (s, 2H), 4.33 (s, 2H), 3.53 (t, J=4.6 Hz, 4H), 3.24 (q, J=6.5 Hz,2H), 2.38-2.32 (m, 6H).

The condensation of 2i was performed as described above in ReactionScheme 1G. The reaction mixture was concentrated almost to dryness andEt₂O (100 mL) was added. The mixture was vigorously stirred for 0.5 h.The solids which formed were collected by filtration to afford 3f (6.14g, quantitative) as a pale yellow solid: ¹H NMR (300 MHz, DMSO-d₆) δ10.86 (br s, 1H), 7.98-7.94 (m, 1H), 7.48-7.42 (m, 2H), 7.34-7.20 (m,4H), 7.11-7.02 (m, 2H), 6.85-6.81 (m, 1H), 4.48 (s, 2H), 3.52 (t, J=4.6Hz, 4H), 3.23 (q, J=6.5 Hz, 2H), 2.35-2.34 (m, 6H).

The cyclization of 3f was performed as described above in ReactionScheme 1G to afford 4f (0.90 g, 45%) as an off-white solid: ¹H NMR (300MHz, DMSO-d₆) δ 11.15 (s, 1H), 8.65 (s, 1H), 7.88-7.84 (m, 1H), 7.28 (s,1H), 7.08-7.01 (m, 2H), 6.33-6.30 (m, 1H), 5.85 (s, 2H), 4.38 (s, 2H),3.52 (t, J=4.5 Hz, 4H), 3.30-3.21 (m, 2H), 2.38-2.32 (m, 6H).

The acylation of 4f was performed as described above in Reaction Scheme1G. The mixture was concentrated to approximately 15 mL and poured intoa mixture of water (50 mL) and saturated NaHCO₃ (50 mL). The aqueousmixture was extracted with EtOAc (2×75 mL) and the combine organics werewashed with brine (30 mL), dried (Na₂SO₄), and concentrated underreduced pressure. The crude product was slurried in acetone and filteredto afford5-amino-1-(3-methylphenyl)carbonyl-3-[3-[2-(4-morpholinyl)ethylaminocarbonylmethoxy]phenyl]amino-1H-1,2,4-triazole(Ia-18) (0.28 g, 42%) as a yellow solid: R_(f) 0.51 (9:1 methylenechloride/methanol); mp 145-147° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.35 (s,1H), 8.02 (s, 1H), 7.98-7.95 (m, 1H), 7.85-7.82 (m, 3H), 7.50-7.46 (m,2H), 7.29-7.28 (m, 1H), 7.15-7.07 (m, 2H), 6.46-6.42 (m, 1H), 4.36 (s,2H), 3.52 (t, J=4.5 Hz, 4H), 3.25 (q, J=6.5 Hz, 2H), 2.41 (s, 3H),2.38-2.32 (m, 6H); ¹³C NMR (75 MHz, DMSO-d₆) δ 165.8, 164.9, 156.5,156.4, 155.6, 140.5, 135.6, 131.4, 130.9, 129.2, 127.6, 126.2, 125.8,108.4, 104.3, 102.0, 65.3, 64.5, 55.3, 51.4, 33.7, 19.2; IR (ATR) 3433,3249, 3197, 1667 cm⁻¹; APCI MS m/z 480 [C₂₄H₂₉N₇O₄+H]⁺; HPLC (Method 2)97.6% (AUC), t_(R)=8.99 min. Anal. Calcd for C₂₄H₂₉N₇O₄: C, 60.11; H,6.10; N, 20.45. Found: C, 60.22; H, 5.92; N, 20.41.

Alternatively, the alkylation of 3-nitrophenol 11 was performed asdescribed above in Reaction Scheme 1I using 20, as prepared below inReaction Scheme 1K, to afford 16b (6.20 g, 99%) as a brown, gummy solid:¹H NMR (300 MHz, DMSO-d₆) δ 7.83-7.80 (m, 1H), 7.73 (t, J=2.3 Hz, 1H),7.57 (t, J=8.2 Hz, 1H), 7.42-7.39 (m, 1H), 5.04 (s, 2H), 3.43-3.32 (m,8H), 1.41 (s, 9H).

The reduction of 16b was performed as described as described above inReaction Scheme 1I to afford 2j (5.79 g, quantitative) as an off-white,gummy solid: ¹H NMR (300 MHz, DMSO-d₆) δ 6.87 (t, J=8.0 Hz, 1H),6.17-6.05 (m, 3H), 5.05 (s, 2H), 4.67 (s, 2H), 3.45-3.31 (m, 8H), 1.41(s, 9H).

The condensation of 2j was performed as described above in ReactionScheme 1G to afford 3g (7.00 g, 86%) as a white solid: ¹H NMR (300 MHz,DMSO-d₆) δ 10.85 (s, 1H), 7.46-7.41 (m, 2H), 7.31-7.26 (m, 4H),7.06-7.03 (m, 2H), 6.81-6.78 (m, 1H), 4.84 (s, 2H), 3.40-3.28 (m, 8H),1.41 (s, 9H).

The cyclization of 3g was performed as described above in ReactionScheme 1G. The mixture was concentrated almost to dryness and Et₂O (100mL) was added. The mixture was stirred vigorously at 0° C. for 1 h andthe solids were collected by filtration to afford 4g (5.67 g, 93%) as awhite solid: ¹H NMR (300 MHz, DMSO-d₆) δ 11.12 (s, 1H), 8.60 (s, 1H),7.19 (s, 1H), 7.06-7.02 (m, 2H), 6.31-6.29 (m, 1H), 5.85 (s, 2H), 4.71(s, 2H), 3.45-3.26 (m, 8H), 1.41 (s, 9H).

The acylation of 4g was performed as described above in Reaction Scheme1G with m-toluoyl chloride 22. The mixture was concentrated almost todryness and water (50 mL) was added. The mixture was stirred vigorouslyfor 1 h, the solids that formed were collected by filtration andpurified by trituration with acetonitrile to afford5-amino-1-(3-methylphenyl)carbonyl-3-[3-(N-tert-butoxycarbonyl)piperazin-4-ylcarbonylmethoxy)phenyl]amino-1H-1,2,4-triazole(Ia-19) (0.68 g, 75%) as a yellow solid: R_(f) 0.56 (9:1 methylenechloride/methanol); mp 206-208° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.32 (s,1H), 8.04 (s, 1H), 7.95-7.93 (m, 1H), 7.81 (s, 2H), 7.48-7.40 (m, 2H),7.23 (s, 1H), 7.13-7.04 (m, 2H), 6.43-6.40 (m, 1H), 4.69 (s, 2H),3.43-3.27 (m, 8H), 2.41 (s, 3H), 1.41 (s, 9H); ¹³C NMR (75 MHz, DMSO-d₆)δ 166.9, 166.3, 158.7, 158.4, 157.6, 154.0, 142.3, 137.5, 133.3, 132.9,131.2, 129.5, 128.1, 127.8, 110.2, 105.9, 104.1, 79.5, 66.3, 44.3, 41.3,28.3, 21.1; IR (ATR) 3421, 3128, 1694, 1654 cm⁻¹; APCI MS m/z 536[C₂₇H₃₃N₇O₅+H]⁺; HPLC (Method 2) 99.0% (AUC), t_(R)=13.72 min. Anal.Calcd for C₂₇H₃₃N₇O₅: C, 60.55; H, 6.21; N, 18.31. Found: C, 60.52; H,6.03; N, 18.35.

Compounds 18 and 20, as set forth below in Reaction Scheme 1K, arealkylating agents used above in Reaction Scheme 1J for compounds of RXand are prepared as illustrated below in Reaction Scheme 1K.

In particular, a mixture of 2-morpholin-4-yl-ethylamine hydrochloride 17(5.0 g, 38.4 mmol) and Et₃N (4.31 g, 42.2 mmol) in THF (60 mL) wascooled to 0° C. and chloroacetyl chloride (4.34 g, 38.4 mmol) was addeddropwise over 2-3 min. The reaction mixture was stirred at 0° C. for 1 hand then at ambient temperature for 20 h. The mixture was filtered,concentrated, and the residue partitioned between EtOAc (75 mL) andwater (25 mL). The organic solution was dried (Na₂SO₄) and concentratedto afford 18 (5.92, 72%) as a brown oil: ¹H NMR (300 MHz, DMSO-d₆) δ8.14 (br s, 1H), 4.06 (s, 2H), 3.56 (t, J=4.6 Hz, 4H), 3.21 (q, J=6.6Hz, 2H), 2.38-2.33 (m, 6H).

Alternatively, a mixture of piperazine-1-carboxylic acid tert-butylester 19 (3.10 g, 16.6 mmol) and Et₃N (1.76 g, 17.4 mmol) in THF (40 mL)was cooled to 0° C. and chloroacetyl chloride (1.87 g, 16.6 mmol) wasadded dropwise over 2-3 min. The reaction mixture was stirred at 0° C.for 1 h and then at ambient temperature for 20 h. The mixture wasfiltered, concentrated and the residue was partitioned between EtOAc (75mL) and water (25 mL). The organic extract was dried (Na₂SO₄) andconcentrated to afford 20 (4.80 g, quantitative) as a brown oil: ¹H NMR(300 MHz, DMSO-d₆) δ 4.39 (s, 2H), 3.43-3.42 (m, 4H), 3.35-3.30 (m, 4H),1.41 (s, 9H).

Compound (Ia-20), as set forth below in Reaction Scheme 1L, is acompound of formula (Ia), as set forth above in the Summary of theInvention, and is prepared as illustrated below in Reaction Scheme 1L.The corresponding compound of formula (Ib) of this compound may beprepared in a similar manner.

Compound (Ia-19) was prepared by the method disclosed above in ReactionScheme 1J.

In particular, the deprotection of5-amino-1-(3-methylphenyl)carbonyl-3-[3-(N-tert-butoxycarbonyl)piperazin-4-ylcarbonylmethoxy)phenyl]amino-1H-1,2,4-triazole(Ia-19) was performed under standard acidic conditions, such as TFA andmethylene chloride. The solvents were removed under reduced pressure andthe residue was dissolved in CH₂Cl₂ (20 mL) and evaporated to dryness(3×). The crude solid was partitioned between EtOAc (35 mL) andsaturated NaHCO₃ (15 mL). The organic layer was separated, washed withbrine (20 mL), dried, and concentrated to afford5-amino-1-(3-methylphenyl)carbonyl-3-[3-(piperazin-4-ylcarbonylmethoxy)phenyl]amino-1H-1,2,4-triazole(Ia-20) (0.19 g, 93%) as a yellow solid: R_(f) 0.35 (9:1 methylenechloride/methanol); mp 169-171° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.32 (s,1H), 8.04 (s, 1H), 7.95-7.92 (m, 1H), 7.82 (s, 2H), 7.46-7.43 (m, 2H),7.24 (s, 1H), 7.12-7.03 (m, 2H), 6.42-6.39 (m, 1H), 4.65 (s, 2H),3.37-3.29 (m, 5H), 2.64 (br s, 4H), 2.41 (s, 3H); ¹³C NMR (75 MHz,DMSO-d₆) δ 164.7, 163.7, 156.6, 156.2, 155.4, 140.1, 135.3, 131.2,130.7, 129.0, 127.3, 125.9, 125.6, 108.0, 103.7, 101.9, 64.2, 43.8,43.4, 40.5, 19.0; IR (ATR) 3427, 3127, 1680, 1647 cm⁻¹; APCI MS m/z 436[C₂₂H₂₅N₇O₃+H]⁺; HPLC (Method 1) 97.8% (AUC), t_(R)=8.65 min.

Compounds (Ia-21), (Ia-22), (Ia-23) and (Ia-24), as set forth below inReaction Scheme 1M, are compounds of formula (Ia), as set forth above inthe Summary of the Invention, and are prepared as illustrated below inReaction Scheme 1M. For purposes of convenience, the minor products,i.e., the corresponding compounds of formula (Ib), are not illustratedin Reaction Scheme 1M, but it is understood that these compounds areprepared as well by the method disclosed therein and can be isolated andseparated from compounds (Ia-21), (Ia-22), (Ia-23) and (Ia-24) bystandard isolation and separation techniques.

In general, compounds (Ia-21), (Ia-22), (Ia-23) and (Ia-24) are preparedfrom compound 1 and compounds 2k, 2l, 2m and 2n, as set forth above inReaction Scheme 1M. Compound 1 and compounds 2k, 2l, 2m and 2n arecommercially available or can be prepared by the methods disclosedherein or by methods known to one skilled in the art. Compound 8 iscommercially available or can be prepared by methods known to oneskilled in the art.

Specifically, a mixture of (3-aminophenoxy)acetonitrile 2k (1.0 g, 6.70mmol) and diphenylcyanocarbimidate 1 (1.64 g, 6.90 mmol) in 2-PrOH (20mL) was stirred at ambient temperature under N₂ for 8 h. The solids thatformed were collected by filtration and washed with 2-PrOH, to afford 3h(1.76 g, 88%) as a white solid: ¹H NMR (300 MHz, DMSO-d₆) δ 10.94 (s,1H), 7.50-7.37 (m, 3H), 7.34-7.27 (m, 3H), 7.23-7.17 (m, 2H), 6.99-6.95(m, 1H), 5.18 (s, 2H).

A mixture of 3h (1.76 g, 6.00 mmol) and hydrazine monohydrate (0.30 g,6.00 mmol) in MeOH (30 mL) was stirred at ambient temperature for 20 h.The MeOH was removed under reduced pressure and the crude material waspartitioned between EtOAc (75 mL) and water (75 mL). The aqueous layerwas extracted with EtOAc (50 mL) and the combined organics were washedwith brine (40 mL), dried (Na₂SO₄) and concentrated to give the crudeproduct. Purification by trituration with CH₂Cl₂ afforded 4h (1.28 g,93%) as a white solid: ¹H NMR (300 MHz, DMSO-d₆) δ 11.18 (s, 1H), 8.75(s, 1H), 7.37-7.32 (m, 1H), 7.13-7.11 (m, 2H), 6.45-6.41 (m, 1H), 5.89(s, 2H), 5.06 (s, 2H).

To an ice-cold mixture of 4h (0.50 g, 2.17 mmol) and pyridine (0.18 g,2.28 mmol) in acetone (35 mL) under N₂ was added dropwise a solution of4-isopropoxybenzoyl chloride 8 (0.45 g, 2.28 mmol) in acetone (5 mL)over 2 min and the resulting solution was stirred at ambient temperaturefor 20 h. The acetone was removed under reduced pressure and the residuewas partitioned between EtOAc (100 mL) and water (100 mL). The aqueouslayer was extracted with EtOAc (30 mL) and the combined organic extractswere washed with brine (50 mL), dried (Na₂SO₄), and concentrated to givethe crude product. Purification by trituration with CH₃CN afforded5-amino-3-[3-(cyanomethoxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole(Ia-21) (0.62 g, 71%) as a white solid: R_(f) 0.65 (9:1 CH₂Cl₂/MeOH);nip (DSC) 210.6-211.7° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.45 (s, 1H),8.25 (d, J=8.9 Hz, 2H), 7.80 (s, 2H), 7.42-7.40 (m, 1H), 7.25-7.13 (m,2H), 7.07 (d, J=8.9 Hz, 2H), 6.59-6.55 (m, 1H), 5.08 (s, 2H), 4.83-4.75(m, 1H), 1.33 (d, J=6.0 Hz, 6H); ¹³C NMR (75 MHz, DMSO-d₆) δ 165.6,161.0, 157.8, 157.3, 156.8, 142.3, 133.0, 129.5, 123.9, 116.5, 114.3,111.0, 105.5, 103.5, 69.6, 53.3, 21.5; IR (ATR) 3421, 3357, 3103, 1676cm⁻¹; APCI MS m/z 393 [C₂₀H₂₀N₆O₃+H]⁺; HPLC (Method A) 98.8% (AUC),t_(R)=13.99 min. Anal. Calcd for C₂₀H₂₀N₆O₃: C, 61.21; H, 5.14; N,21.42. Found: C, 61.17; H, 4.88; N, 21.19.

Alternatively, a mixture of 2l (1.68 g, 7.56 mmol) anddiphenylcyanocarbimidate 1 (1.80 g, 7.56 mmol) in 2-PrOH (20 mL) wasstirred at ambient temperature under N₂ for 20 h. The solids that formedwere collected by filtration and washed with 2-PrOH, to afford 3i (2.04g, 74%) as a yellow-white solid: ¹H NMR (300 MHz, DMSO-d₆) δ 10.82 (brs, 1H), 7.50-7.26 (m, 6H), 7.09-7.01 (m, 2H), 6.85-6.73 (m, 1H), 4.08(t, J=5.7 Hz, 2H), 3.58-3.55 (m, 4H), 2.70 (t, J=5.7 Hz, 2H), 2.50-2.46(m, 4H).

A mixture of 3i (2.03 g, 5.50 mmol) and hydrazine monohydrate (0.28 g,5.50 mmol) in MeOH (30 mL) was stirred at ambient temperature for 4 h.The MeOH was removed under reduced pressure and the residue was slurriedin EtOAc and filtered to afford 4i (1.35 g, 81%) as a white solid: ¹HNMR (300 MHz, DMSO-d₆) δ 11.13 (s, 1H), 8.58 (s, 1H), 7.24 (s, 1H),7.05-6.85 (m, 2H), 6.30 (d, J=7.5 Hz, 1H), 5.86 (s, 2H), 4.00 (t, J=5.7Hz, 2H), 3.70-3.47 (m, 4H), 2.67 (t, J=5.7 Hz, 2H), 2.50-2.22 (m, 4H).

To an ice-cold mixture of 4i (0.30 g, 0.98 mmol) and Et₃N (0.10 g, 1.00mmol) in acetone (15 mL) under N₂ was added dropwise a solution of4-isopropoxy benzoyl chloride 8 (0.20 g, 0.98 mmol) in acetone (5 mL)over 2 min and the resulting solution was stirred at ambient temperaturefor 20 h. The acetone was removed under reduced pressure and the residuewas partitioned between EtOAc (50 mL) and water (50 mL). The aqueouslayer was extracted with EtOAc (50 mL) and the combined organics werewashed with brine (50 mL), dried (Na₂SO₄), and concentrated to give thecrude product. Purification by flash chromatography (95:5 CH₂Cl₂/MeOH)afforded5-amino-1-(4-(iso-propoxy)phenylcarbonyl-3-[3-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(Ia-22) (0.23 g, 50%) as a white solid: R_(f) 0.50 (9:1 CH₂Cl₂/MeOH); mp(DSC) 152-153.7° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.29 (s, 1H), 8.25 (d,J=8.9 Hz, 2H), 7.77 (s, 2H), 7.42-7.41 (m, 1H), 7.13-7.05 (m, 3H), 6.92(dd, J=8.0, 1.0 Hz, 1H), 6.41 (dd, J=7.9, 2.0 Hz, 1H), 4.82-4.74 (m,1H), 3.99 (t, J=5.5 Hz, 2H), 3.58-3.55 (m, 4H), 2.64 (t, J=5.5 Hz, 2H),2.45-2.42 (m, 4H), 1.32 (d, J=6.0 Hz, 6H); ¹³C NMR (75 MHz, DMSO-d₆) δ166.0, 161.4, 159.3, 158.3, 157.7, 142.4, 133.4, 129.6, 124.4, 114.8,109.6, 106.5, 103.0, 69.9, 66.4, 65.4, 57.5, 54.0, 22.0; IR (ATR) 3664,1692 cm⁻¹; APCI MS m/z 467 [C₂₄H₃₀N₆O₄+H]⁺; HPLC (Method A) 98.0% (AUC),t_(R)=9.54 min.

Alternatively, a mixture of 2m (2.56 g, 11.6 mmol) anddiphenylcyanocarbimidate 1 (2.77 g, 11.6 mmol) in 2-PrOH (70 mL) wasstirred at ambient temperature under N₂ for 20 h. The 2-PrOH was removedunder reduced pressure and the residue was partitioned between EtOAc (75mL) and water (75 mL). The aqueous layer was extracted with EtOAc (75mL) and the combined organics were dried (Na₂SO₄), and concentrated togive the crude product. Purification by flash chromatography (CH₂Cl₂then 95:5 CH₂Cl₂/MeOH) afforded 3j (3.68 g, 87%) as a beige foam: ¹H NMR(300 MHz, DMSO-d₆) δ 10.36 (br s, 1H), 7.50-7.41 (m, 2H), 7.29-7.23 (m,4H), 7.12-6.96 (m, 2H), 6.80-6.73 (m, 1H), 4.09-4.05 (m, 2H), 2.73-2.69(m, 2H), 2.49-2.42 (m, 4H), 1.54-1.37 (m, 6H).

A mixture of 3j (3.0 g, 8.20 mmol) and hydrazine monohydrate (0.41 g,8.40 mmol) in MeOH (30 mL) was stirred at ambient temperature for 20 h.The MeOH was removed under reduced pressure and the residue waspartitioned between EtOAc (75 mL) and water (75 mL). The aqueous layerwas extracted with EtOAc (75 mL) and the organic layer concentrated toafford 4j (2.00 g, 81%) as a beige foam: ¹H NMR (300 MHz, DMSO-d₆) δ11.16 (s, 1H), 8.58 (s, 1H), 7.24 (s, 1H), 7.05-6.94 (m, 2H), 6.30-6.28(m, 1H), 5.87 (s, 2H), 3.97 (t, J=6.0 Hz, 2H), 2.62 (t, J=6.0 Hz, 2H),2.41-2.39 (m, 4H), 1.53-1.36 (m, 6H).

To an ice-cold mixture of 4j (0.35 g, 1.16 mmol) and Et₃N (0.12 g, 1.18mmol) in acetone (20 mL) under N₂ was added dropwise a solution of4-isopropoxyl benzoylchloride 8 (0.23 g, 1.16 mmol) in acetone (5 mL)over 2 min and the resulting solution was stirred at ambient temperaturefor 20 h. The acetone was removed under reduced pressure and the residuewas partitioned between EtOAc (75 mL) and saturated aqueous NaHCO₃. Theaqueous layer was separated, extracted with EtOAc (75 mL) and thecombined organics were dried (Na₂SO₄) and concentrated to give the crudeproduct. Purification by flash chromatography (95:5 CH₂Cl₂/MeOH)afforded5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[3-(piperidin-1-yl)phenylamino]-1H-1,2,4-triazole(Ia-23) (0.19 g, 35%) as a yellow solid: R_(f) 0.25 (9:1 CH₂Cl₂/MeOH);mp 121-124° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.29 (s, 1H), 8.25 (d, J=8.8Hz, 2H), 7.77 (s, 2H), 7.40 (s, 1H), 7.13-7.05 (m, 3H), 6.94-6.91 (m,1H), 6.42-6.40 (m, 1H), 4.79-4.75 (m, 1H), 3.99 (br s, 2H), 2.63 (br s,2H), 2.41 (br s, 4H), 1.50 (br s, 4H), 1.38-1.30 (m, 8H); ¹³C NMR (75MHz, DMSO-d₆) δ 166.0, 161.4, 159.3, 158.3, 157.7, 142.4, 133.4, 129.6,124.3, 114.8, 109.7, 106.5, 103.1, 69.9, 65.5, 57.6, 54.6, 25.6, 24.1,22.0; IR (ATR) 3329, 1671 cm⁻¹; APCI MS m/z 465 [C₂₅H₃₂N₆O₃+H]⁺; HPLC(Method A) 97.7% (AUC), t_(R)=10.19 min.

Alternatively, a mixture of 2n (4.46 g, 21.3 mmol) anddiphenylcyanocarbimidate (5.07 g, 21.3 mmol) in 2-PrOH (100 mL) wasstirred at ambient temperature under N₂ for 20 h. The solids that formedwere collected by filtration and washed with 2-PrOH to afford 3k (5.90g, 78%) as an off-white solid: ¹H NMR (300 MHz, DMSO-d₆) δ 10.82 (s,1H), 7.50-7.37 (m, 2H), 7.32-7.26 (m, 4H), 7.08-7.03 (m, 2H), 6.82 (dd,J=7.9, 1.9 Hz, 1H), 4.98 (t, J=4.9 Hz, 1H), 4.07 (t, J=6.5 Hz, 2H),3.93-3.76 (m, 4H), 2.06-2.00 (m, 2H).

A mixture of 3k (3.0 g, 8.50 mmol) and hydrazine monohydrate (0.43 g,8.67 mmol) in MeOH (40 mL) was stirred at ambient temperature for 20 h.The MeOH was removed under reduced pressure and the residue waspartitioned between EtOAc (75 mL) and water (75 mL). The aqueous layerwas extracted with EtOAc (75 mL) and the combined organics were washedwith brine (50 mL), dried (Na₂SO₄), and concentrated. Purification byflash chromatography (CH₂Cl₂ to 95:5 CH₂Cl₂/MeOH) afforded 4k (1.90 g,65%) as a white solid: ¹H NMR (300 MHz, DMSO-d₆) δ 11.13 (s, 1H), 8.78(s, 1H), 7.58 (s, 1H), 7.05-6.95 (m, 2H), 6.30-6.27 (m, 1H), 5.86 (s,2H), 4.97 (t, J=4.9 Hz, 1H), 3.99 (t, J=6.5 Hz, 2H), 3.93-3.76 (m, 4H),2.04-1.98 (m, 2H).

To an ice-cold mixture of 4k (0.50 g, 1.70 mmol) and pyridine (0.16 g,2.05 mmol) in acetone (35 mL) under N₂ was added dropwise a solution of4-isopropoxybenzoyl chloride 8 (0.37 g, 1.87 mmol) in acetone (5 mL)over 2 min and the resulting solution was stirred at ambient temperaturefor 20 h. The acetone was removed under reduced pressure and the residuewas partitioned between EtOAc (75 mL) and water (75 mL). The aqueouslayer was extracted with EtOAc (75 mL) and the combined organics werewashed with brine (40 mL), dried (Na₂SO₄), and concentrated to give thecrude product. Purification by trituration with CH₃CN afforded5-amino-3-[3-[2-(1,3-dioxolan-2-yl)ethoxy]phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole(Ia-24) (0.51 g, 35%) as an off-white solid: R_(f) 0.61 (9:1CH₂Cl₂/MeOH); mp (DSC) 144.4-145.4° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.31(s, 1H), 8.25 (d, J=8.8 Hz, 2H), 7.78 (s, 2H), 7.40 (s, 1H), 7.14-7.03(m, 3H), 6.95 (dd, J=8.1, 1.0 Hz, 1H), 6.41 (dd, J=7.9, 2.1 Hz, 1H),4.97 (t, J=5.1 Hz, 1H), 4.81-4.73 (m, 1H), 3.98 (t, J=6.3 Hz, 2H),3.93-3.76 (m, 4H), 2.02-1.96 (m, 2H), 1.32 (d, J=6.0 Hz, 6H); ¹³C NMR(75 MHz, DMSO-d₆) δ 166.0, 161.4, 159.3, 158.3, 157.7, 142.5, 133.4,129.6, 124.3, 114.8, 109.7, 106.5, 103.0, 101.5, 70.0, 64.6, 63.5, 33.8,22.0; IR (ATR) 3417, 3355, 3115, 1678 cm⁻¹; APCI MS m/z 454[C₂₃H₂₇N₆O₆+H]⁺; HPLC (Method A)>99% (AUC), t_(R)=14.59 min. Anal. Calcdfor C₂₃H₂₇N₆O₅: C, 60.92; H, 6.00; N, 15.44. Found: C, 60.71; H, 5.89;N, 15.32.

In a manner similar to that described above in the preparation of(Ia-21), (Ia-22), (Ia-23), and (Ia-24), a solution of4-isopropoxybenzoyl chloride 8 (0.37 g, 1.86 mmol) in acetone (5 mL) wasadded dropwise over 2 min under N₂ to an ice-cold mixture of triazole 2i(0.26 g, 0.92 mmol), prepared as described above in Reaction Scheme 1J,and pyridine (0.08 g, 0.92 mmol) in acetone (15 mL) and the resultingsolution was stirred at ambient temperature for 40 h. The solids thatformed were collected by filtration and triturated with acetone toafford5-amino-3-[3-(benzyloxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole(Ia-25) (0.10 g, 24%) as a white solid: R_(f) 0.57 (9:1 CH₂Cl₂/MeOH); mp(DSC) 188.7-189.9° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.35 (s, 1H), 8.27(d, J=8.8 Hz, 2H), 7.78 (s, 2H), 7.58 (s, 1H), 7.43-7.33 (m, 5H), 7.12(t, J=8.1 Hz, 1H), 6.99-6.91 (m, 3H), 6.50-6.47 (m, 1H), 4.98 (s, 2H),4.52-4.42 (m, 1H), 1.19 (d, J=6.0 Hz, 6H); ¹³C NMR (75 MHz, DMSO-d₆) δ166.0, 161.4, 159.3, 158.3, 157.7, 142.5, 137.3, 133.4, 129.6, 128.7,128.3, 128.1, 124.3, 114.8, 109.8, 106.9, 103.1, 69.8, 69.3, 21.9; IR(ATR) 3364, 1671 cm⁻¹; APCI MS m/z 444 [C₂₅H₂₅N₅O₃+H]⁺; HPLC (MethodA)>99% (AUC), t_(R)=16.51 min. Anal. Calcd for C₂₅H₂₅N₅O₃: C, 66.70; H,5.68; N, 15.79. Found: C, 67.42; H, 5.71; N, 15.63.

Compounds (Ia-26) and (Ia-27), as set forth below in Reaction Scheme 1N,are compounds of formula (Ia), as set forth above in the Summary of theInvention, and are prepared as illustrated below in Reaction Scheme 1N.For purposes of convenience, the minor products, i.e., the correspondingcompounds of formula (Pb), are not illustrated in Reaction Scheme 1N,but it is understood that these compounds are prepared as well by themethod disclosed therein and can be isolated and separated fromcompounds (Ia-26) and (Ia-27) by standard isolation and separationtechniques.

In general, compounds (Ia-26) and (Ia-27) are prepared from compounds 4iand compounds 21 and 22, respectively. Compound 4i can be prepared bymethods described herein or by methods known to one skilled in the art.Compounds 21 and 22 are commercially available or can be prepared bymethods known to one skilled in the art.

Specifically, to an ice-cold mixture of 4i (0.30 g, 0.98 mmol) andpyridine (0.08 g, 1.00 mmol) in acetone (25 mL) under N₂ was addeddropwise benzoyl chloride 21 (0.14 g, 0.98 mmol) over 2 min and theresulting solution was stirred at ambient temperature for 4 h. Theacetone was removed under reduced pressure and the residue waspartitioned between EtOAc (50 mL) and water (50 mL). The organic layerwas washed with brine (50 mL), dried (Na₂SO₄), and concentrated to givethe crude product which was triturated with EtOAc to afford5-amino-3-[3-[2-(morpholin-4-yl)ethoxy]phenylamino]-1-phenylcarbonyl-1H-1,2,4-triazole,hydrogen chloride salt (Ia-26) (0.23 g, 50%) as a yellow solid: R_(f)0.54 (9:1 CH₂Cl₂/MeOH); mp (DSC) 236.6-242.1° C.; ¹H NMR (300 MHz,DMSO-d₆) δ 9.39 (s, 1H), 8.15-8.12 (m, 2H), 7.84 (s, 2H), 7.69-7.66 (m,1H), 7.59 (t, J=7.7 Hz, 2H), 7.32 (s, 1H), 7.13 (t, J=8.1 Hz, 1H),7.04-7.01 (m, 1H), 6.48 (dd, J=7.7, 1.7 Hz, 1H), 4.29 (s, 2H), 3.96-3.79(m, 4H), 3.48-3.38 (m, 5H), 3.21-3.16 (m, 2H); ¹³C NMR (75 MHz, DMSO-d₆)δ 164.9, 156.3, 156.2, 155.5, 140.4, 131.1, 130.7, 128.4, 127.6, 126.2,108.3, 104.5, 101.1, 61.3, 60.2, 53.2, 49.9; IR (ATR) 3685, 3393, 1678cm⁻¹; APCI MS m/z 409 [C₂₁H₂₄N₆O₃+H]⁺; HPLC (Method A) 98.6% (AUC),t_(R)=8.55 min. Anal. Calcd for C₂₁H₂₄N₆O₃.HCl: C, 56.69; H, 5.66; N,18.89. Found: C, 56.51; H, 5.62; N, 18.68.

Alternatively, to an ice-cold mixture of 4i (0.30 g, 0.98 mmol) andpyridine (0.08 g, 1.00 mmol) in acetone (15 mL) under N₂ was addeddropwise m-toluoyl chloride 22 (0.15 g, 0.98 mmol) over 2 min and theresulting solution was stirred at ambient temperature for 4 h. Theacetone was removed under reduced pressure and the residue waspartitioned between EtOAc (50 mL) and water (50 mL). The organic layerwas washed with brine (50 mL), dried (Na₂SO₄), and concentrated to givethe crude product which was purified by flash chromatography (95:5CH₂Cl₂/MeOH) followed by trituration with CH₂Cl₂ to afford5-amino-1-(3-(methyl)phenylcarbonyl-3-[3-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(Ia-27) (0.17 g, 41%) as a yellow solid: R_(f) 0.50 (9:1 CH₂Cl₂/MeOH);mp 60-63° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.30 (s, 1H), 7.99-7.93 (m,2H), 7.81 (s, 2H), 7.49-7.37 (m, 2H), 7.32 (s, 1H), 7.08 (t, J=8.1 Hz,1H), 6.96-6.93 (m, 1H), 6.41 (dd, J=7.9, 1.7 Hz, 1H), 3.93 (t, J=5.5 Hz,2H), 3.57-3.54 (m, 4H), 2.62 (t, J=5.5 Hz, 2H), 2.42 (s, 7H); ¹³C NMR(75 MHz, DMSO-d₆) δ 167.0, 159.3, 158.4, 157.6, 142.4, 137.5, 133.3,133.0, 131.1, 129.5, 128.1, 127.7, 109.7, 106.3, 103.4, 66.5, 65.3,57.4, 53.9, 21.2; IR (ATR) 3706, 3680, 3428, 3291, 1676 cm⁻¹; APCI MSm/z 423 [C₂₂H₂₆N₆O₃+H]⁺; HPLC (Method A) 98.2% (AUC), t_(R)=8.96 min.

Compounds (Ia-28) and (Ia-29), as set forth below in Reaction Scheme 2,are compounds of formula (Ia), as set forth above in the Summary of theInvention, and are prepared as illustrated below in Reaction Scheme 2.For purposes of convenience, the minor products, i.e., the correspondingcompounds of formula (Ib), are not illustrated in Reaction Scheme 2, butit is understood that these compounds are prepared as well by the methoddisclosed therein and can be isolated and separated from compounds(Ia-28) and (Ia-29) by standard isolation and separation techniques.

In general, compounds (Ia-28) and (Ia-29) are prepared from compounds23, 26, 1 and 22, as described above in Reaction Scheme 2. Compounds 23,26, 1 and 22 are commercially available or can be prepared by methodsknown to one skilled in the art.

Specifically, a mixture of 23 (4.0 g, 17.0 mmol), MeOH (0.82 g, 25.5mmol) and lithium borohydride (0.56 g, 25.5 mmol) in ether (80 mL) wasstirred at ambient temperature for 4 h. The mixture was diluted withethyl acetate and washed with 1 N HCl and brine, dried (MgSO₄), andconcentrated to afford 24 (3.08 g, 87%) as a yellow solid: ¹H NMR (300MHz, DMSO-d₆) δ 8.59 (d, J=2.4 Hz, 1H), 8.19 (dd, J=9.0, 2.5 Hz, 1H),7.80 (d, J=9.0 Hz, 1H), 7.00 (s, 1H), 5.65 (t, J=5.9 Hz, 1H), 4.63 (d,J=5.6 Hz, 2H).

A mixture of 24 (3.85 g, 19.9 mmol), carbon tetrabromide (9.25 g, 27.9mmol) and triphenylphosphine (7.32 g, 27.9 mmol) in CH₂Cl₂ was stirredat ambient temperature for 1.5 h. The reaction mixture was concentratedto afford a residue which was purified by flash chromatography (silica,1:10 ethyl acetate/hexanes) to afford 25 (4.24 g, 83%) as a white solid:¹H NMR (300 MHz, DMSO-d₆) δ 8.64 (d, J=2.4 Hz, 1H), 8.25 (dd, J=9.1, 2.5Hz, 1H), 7.85 (d, J=9.1 Hz, 1H), 7.26 (s, 1H), 4.97 (s, 2H).

To a stirred ice cold mixture of N-methylallylamine 26 (2.09 g, 29.4mmol) and potassium carbonate (2.43 g, 17.6 mmol) in acetonitrile (37mL) was added dropwise a solution of 25 (3.76 g, 14.7 mmol) inacetonitrile (37 mL) over a period of 30 min. After stirring for 1.5 hin an ice-bath and an additional 22 h at ambient temperature, thereaction mixture was partitioned between methylene chloride and water.The organic layer was separated washed with brine, dried (MgSO₄), andconcentrated to afford 27 (3.11 g, 86%) as a yellow oil: ¹H NMR (300MHz, DMSO-d₆) δ 8.58 (d, J=2.3 Hz, 1H), 8.18 (dd, J=9.0, 2.4 Hz, 1H),7.81 (d, J=9.0 Hz, 1H), 7.02 (s, 1H), 5.90-5.80 (m, 1H), 5.30-5.10 (m,2H), 3.74 (s, 2H), 3.08 (d, J=6.3 Hz, 2H), 2.21 (s, 3H).

To a solution of 27 (1.81 g, 7.35 mmol) in 10:1 HOAc/water (22 mL) at55° C. was added iron powder (2.46 g, 44.1 mmol) portionwise over 5 minand the mixture stirred at 55° C. for 3 h. The reaction mixture wasdiluted with ethyl acetate (100 mL), filtered through diatomaceous earthand the filtrate concentrated. The residue was taken up into ethylacetate, the ethyl acetate solution washed with water, brine, dried(MgSO₄), and concentrated to afford 28 (0.56 g, 35%) as an amber oil:ESI MS m/z 217 [C₁₃H₁₆N₂O+H]⁺.

A mixture of 28 (0.66 g, 3.05 mmol) and diphenylcyanocarbimidate 1 (0.73g, 3.05 mmol) in 2-PrOH (7 mL) was stirred at ambient temperature underN₂ for 22 h. The solids that formed were collected by filtration andwashed with 2-PrOH to afford 29 (0.59 g, 54%) as a tan solid: ¹H NMR(300 MHz, DMSO-d₆) δ 10.83 (br s, 1H), 7.70-7.20 (m, 8H), 6.81 (s, 1H),5.90-5.80 (m, 1H), 5.30-5.10 (m, 2H), 3.68 (s, 1H), 3.06 (d, J=6.3 Hz,2H), 2.19 (s, 3H).

A mixture of 29 (0.59 g, 1.64 mmol) and hydrazine monohydrate (0.12 g,2.45 mmol) in MeOH (6 mL) was stirred at ambient temperature for 20 h.The reaction mixture was concentrated and the residue obtained waspurified by flash chromatography (silica, 9:1 methylenechloride/methanol) to afford 30 (0.40 g, 82%) as an off-white foam: ¹HNMR (300 MHz, DMSO-d₆) δ 11.06 (br s, 1H), 8.51 (br s, 1H), 7.83 (d,J=1.2 Hz, 1H), 7.35-7.20 (m, 2H), 6.62 (s, 1H), 6.0-5.57 (m, 3H),5.30-5.10 (m, 2H), 3.61 (s, 2H), 3.04 (d, J=6.4 Hz, 2H), 2.18 (s, 3H).

To a stirred, ice-cold mixture of 30 (0.40 g, 1.34 mmol) andtriethylamine (0.14 g, 1.34 mmol) in acetone (8 mL) was added m-toluoylchloride 22 (0.21 g, 1.34 mmol). After stirring for 1 h in an ice-bathand an additional 20 h at ambient temperature, the reaction mixture waspartitioned between saturated Na₂CO₃ (40 mL) and ethyl acetate (40 mL).The organic layer was separated, washed with brine, dried (MgSO₄), andconcentrated to afford a yellow oil. Purification by flashchromatography (silica, 1:1 ethyl acetate/hexanes then 2:1 ethylacetate/hexanes) gave5-amino-3-(2-((allyl(methyl)amino)methyl)benzofuran-5-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole(Ia-28) (0.192 g, 34%) as a yellow solid: R_(f) 0.36 (95:5 methylenechloride/methanol); mp 128-131° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.27 (s,1H), 8.12 (s, 1H), 7.97 (d, J=5.8 Hz, 1H), 7.86-7.80 (m, 3H), 7.50-7.30(m, 4H), 6.58 (s, 1H), 5.90-5.81 (m, 1H), 5.24-5.14 (m, 2H), 3.64 (s,2H), 3.04 (d, J=6.2 Hz, 2H), 2.45 (s, 3H), 2.18 (s, 3H); ¹³C NMR (75MHz, DMSO-d₆) δ 166.6, 158.6, 157.5, 156.2, 149.3, 137.2, 136.8, 135.9,133.3, 132.8, 131.2, 128.3, 128.0, 127.6, 117.7, 114.6, 110.8, 107.8,105.3, 59.6, 53.2, 41.6, 21.1; IR (ATR) 1672, 1584, 1558 cm¹; ESI MS m/z417 [C₂₃H₂₄N₆O₂+H]⁺; HPLC (Method 2) 96.9% (AUC), t_(R)=9.59 min.

A mixture of bis(dibenzylideneacetone)palladium(0) (0.0061 g, 0.011mmol) and 1,4-bis(diphenylphosphino)butane (0.0045 g, 0.011 mmol) in THF(2 mL) was stirred at ambient temperature for 15 minutes, then added toa stirred solution of (Ia-28) (0.088 g, 0.211 mmol) and thiosalicyclicacid (0.036 g, 0.232 mmol) in THF (4 mL). After stirring for 30 h atambient temperature, additional bis(dibenzylideneacetone)palladium(0.012 g, 0.022 mmol) and 1,4-bis(diphenylphosphino)butane (0.009 g,0.022 mmol) in THF (2 mL) was added. The reaction was stirred anadditional 20 h at ambient temperature, then diluted with ethyl acetate.The organic solution was washed with 1 N NaOH, and brine, dried (MgSO4),and concentrated to afford a yellow-orange residue. Purification byflash chromatography (silica, 95:5 methylene chloride/methanol) followedby preparative TLC (silica, 9:1 methylene chloride/methanol) gave5-amino-3-(2-((methylamino)methyl)benzofuran-5-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole(Ia-29) (0.019 g, 19%) as a pale yellow solid: R_(f) 0.35 (9:1 methylenechloride/methanol); mp 128-131° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.26 (s,1H), 8.11 (s, 1H), 7.96 (d, J=6.3 Hz, 1H), 7.85 (d, J=2.0 Hz, 1H), 7.80(br s, 2H), 7.50-7.48 (m, 2H), 7.37-7.47 (m, 2H), 6.53 (s, 1H), 3.74 (s,2H), 2.46 (s, 3H), 2.30 (s, 3H); IR (ATR) 1675, 1561, 1350 cm¹; ESI MSm/z 377 [C₂₀H₂₀N₆O₂+H]⁺; HPLC (Method 2) 90.4% (AUC), t_(R)=8.79 min.

Compounds (Ia-30), as set forth below in Reaction Scheme 3, arecompounds of formula (Ia), as set forth above in the Summary of theInvention, and are prepared as illustrated below in Reaction Scheme 3wherein R^(1a) is one or more substituents selected from the groupconsisting of halo, haloalkyl, alkyl, optionally substituted heteroaryl,optionally substituted heterocyclyl, —R⁸—OR¹⁰, —R⁸—O—R⁹—OR¹⁰,—R⁸—O—R⁹—O—R⁹—OR¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷,—R⁸—O—R⁹—S(O)_(p)R⁶ (where p is 0, 1 or 2), —R⁸—O—R⁹—N(R⁶)R⁷,—R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and —R⁸—N(R⁶)C(O)R¹⁰, wherein each R⁶, R⁷, R⁸,R⁹, R¹⁰ and R¹¹ are as defined above in the Summary of the Invention andR^(3a) is one or more substituents selected from the group consisting ofhalo, haloalkyl, alkyl, optionally substituted heteroaryl, optionallysubstituted heterocyclyl, —R⁸—OR¹⁰, —R⁸—O—R⁹—OR¹⁰, —R⁸—O—R⁹—O—R⁹—OR¹⁰,—R⁸—O—R⁹—CN, —R⁸—O—R⁹—C(O)OR¹⁰, —R⁸—O—R⁹—C(O)N(R⁶)R⁷,—R⁸—O—R⁹—S(O)_(p)R⁶ (where p is 0, 1 or 2), —R⁸—O—R⁹—N(R⁶)R⁷,—R⁸—O—R⁹—C(NR¹¹)N(R¹¹)H, and —R⁸—N(R⁶)C(O)R¹⁰ where each R⁶, R⁷, R⁸, R⁹,R¹⁰ and R¹¹ is as defined above in the Summary of the Invention. Forpurposes of convenience, the minor products, i.e., the correspondingcompounds of formula (Ib), are not illustrated in Reaction Scheme 3, butit is understood that these compounds are prepared as well by the methoddisclosed therein and can be isolated and separated from compounds(Ia-30) by standard isolation and separation techniques.

In general, compounds (Ia-30) are prepared from compounds 4 and 31 asset forth above in Reaction Scheme 3. Compounds 4 can be prepared bymethods disclosed herein or by methods known to one skilled in the art.Compounds 31 are commercially available or can be prepared by methodsknown to one skilled in the art.

Specifically, a mixture of 3-amino-5-anilino-1,2,4-triazole 4 (1 equiv)and isocyanate 31 (1.5 equiv) in dry THF was stirred at ambienttemperature overnight. The reaction was then quenched with methanol andconcentrated in vacuo. The residue was purified by silica gel columnchromatography in 5% triethylamine/ethyl acetate gave the product(Ia-30).

The method disclosed above in Reaction Scheme 3 can be used to preparethe following compounds, using the appropriately substituted startingmaterials:

5-amino-N-(3-methylphenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #29), as a white solid (33% yield); ¹H-NMR (DMSO-d₆, 300 MHz)9.33 (s, 1H), 8.92 (s, 1H), 7.55 (d, J=9.0 Hz, 2H), 7.46 (s, 1H), 7.42(d, J=7.8 Hz, 1H), 7.29 (s, 2H), 7.23 (t, J=7.8 Hz, 1H), 6.94 (d, J=7.5Hz, 1H), 6.81 (d, J=9.0 Hz, 2H), 3.98 (t, J=6.0 Hz, 2H), 2.60 (t, J=6.0Hz, 2H), 2.41 (m, 4H), 2.31 (s, 3H), 1.47 (m, 4H), 1.37 (m, 2H) ppm; MS(ES) 436.8 (M+H).

5-amino-N-(3-methoxyphenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #30), ¹H-NMR (DMSO-d₆, 300 MHz) 9.37 (s, 1H), 8.92 (s, 1H),7.55 (d, J=9.0 Hz, 2H), 7.27 (m, 5H), 6.81 (d, J=8.4 Hz, 2H), 6.71 (m,1H), 3.98 (t, J=6.0 Hz, 2H), 3.75 (s, 3H), 2.60 (t, J=6.0 Hz, 2H), 2.41(m, 4H), 1.48 (m, 4H), 1.37 (m, 2H) ppm; MS (ES) 452.8 (M+H).

5-amino-N-(3-methylphenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #31), ¹H-NMR (DMSO-d₆, 300 MHz) 9.32 (s, 1H), 8.91 (s, 1H),7.56 (d, J=9.0 Hz, 2H), 7.46 (s, 1H), 7.42 (d, J=7.5 Hz, 1H), 7.28 (s,2H), 7.23 (t, J=7.8 Hz, 1H), 6.94 (d, J=7.5 Hz, 1H), 6.82 (d, J=8.7 Hz,2H), 3.99 (t, J=6.0 Hz, 2H), 2.78 (m, 2H), 2.55 (m, 4H), 2.31 (s, 3H),1.68 (m, 4H) ppm; MS (ES) 422.2 (M+H).

5-amino-N-(3-methoxyphenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #32); ¹H-NMR (DMSO-d₆, 300 MHz) 9.37 (s, 1H), 8.92 (s, 1H),7.55 (d, J=9.0 Hz, 2H), 7.30 (s, 2H), 7.24 (d, J=6.3 Hz, 1H), 7.23 (s,1H), 6.81 (d, J=9.3 Hz, 2H), 6.70 (d, J=6.3 Hz, 1H), 3.98 (t, J=6.0 Hz,2H), 3.75 (s, 3H), 2.74 (t, J=6.0 Hz, 2H), 2.48 (m, 4H), 1.67 (m, 4H)ppm; MS (ES) 438.1 (M+H).

5-amino-N-(3,5-(dimethoxy)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #33), ¹H-NMR (DMSO-d₆, 300 MHz) 9.31 (s, 1H), 8.92 (s, 1H),7.54 (d, J=8.7 Hz, 2H), 7.31 (s, 2H), 6.93 (s, 2H), 6.81 (d, J=8.4 Hz,2H), 6.28 (s, 1H), 3.99 (t, J=6.0 Hz, 2H), 3.73 (s, 6H), 2.60 (t, J=6.0Hz, 2H), 2.42 (m, 4H), 1.48 (m, 4H), 1.37 (m, 2H) ppm; MS (ES) 482.8(M+H).

5-amino-N-(3,5-(dimethoxy)phenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #34), ¹H-NMR (DMSO-d₆, 300 MHz) 9.31 (s, 1H), 8.93 (s, 1H),7.54 (d, J=8.7 Hz, 2H), 7.31 (s, 2H), 6.94 (s, 1H), 6.93 (s, 1H), 6.81(d, J=9.0 Hz, 2H), 6.28 (t, J=2.4 Hz, 1H), 3.98 (t, J=6.0 Hz, 2H), 3.73(s, 6H), 2.75 (t, J=6.0 Hz, 2H), 2.42 (m, 4H), 1.67 (m, 4H) ppm; MS (ES)468.3 (M+H).

5-amino-N-(1,3-benzodioxol-5-yl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #35), ¹H-NMR (DMSO-d₆, 300 MHz) 9.34 (s, 1H), 8.90 (s, 1H),7.55 (d, J=9.0 Hz, 2H), 7.26 (s, 2H), 7.24 (d, J=2.4 Hz, 1H), 7.04 (dd,J=8.1, 2.1 Hz, 1H), 6.89 (d, J=8.4 Hz, 1H), 6.80 (d, J=9.0 Hz, 2H), 6.00(s, 2H), 3.97 (t, J=6.0 Hz, 2H), 2.61 (t, J=6.0 Hz, 2H), 2.41 (m, 4H),1.48 (m, 4H), 1.37 (m, 2H) ppm; MS (ES) 466.1 (M+H).

5-amino-N-(1,3-benzodioxol-5-yl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #36), ¹H-NMR (DMSO-d₆, 300 MHz) 9.34 (s, 1H), 8.91 (s, 1H),8.14 (s, 1H), 7.55 (d, J=8.7 Hz, 2H), 7.24 (s, 2H), 7.03 (d, J=8.4 Hz,1H), 6.89 (d, J=8.4 Hz, 1H), 6.80 (d, J=8.7 Hz, 2H), 6.01 (s, 2H), 3.99(t, J=6.0 Hz, 2H), 2.81 (t, J=6.0 Hz, 2H), 2.57 (m, 4H), 1.69 (m, 4H)ppm; MS (ES) 452.2 (M+H).

5-amino-N-(4-methylphenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #37), ¹H-NMR (DMSO-d₆, 300 MHz) 9.34 (s, 1H), 8.91 (s, 1H),7.56 (d, J=8.4 Hz, 2H), 7.49 (d, J=8.4 Hz, 1H), 7.27 (s, 2H), 7.15 (d,J=8.4 Hz, 1H), 6.81 (d, J=8.7 Hz, 2H), 3.99 (t, J=5.4 Hz, 2H), 2.77 (t,J=5.4 Hz, 2H), 2.49 (m, 4H), 2.28 (s, 3H), 1.68 (m, 4H) ppm; MS (ES)422.2 (M+H).

5-amino-N-(3,4-(dimethyl)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #38), ¹H-NMR (DMSO-d₆, 300 MHz) 9.26 (s, 1H), 8.91 (s, 1H),7.55 (d, J=9.0 Hz, 2H), 7.41 (s, 1H), 7.34 (d, J=8.4 Hz, 1H), 7.27 (s,2H), 7.10 (d, J=8.1 Hz, 1H), 6.81 (d, J=9.0 Hz, 2H), 3.98 (t, J=6.0 Hz,2H), 2.61 (t, J=6.0 Hz, 2H), 2.41 (m, 4H), 2.22 (s, 3H), 2.20 (s, 3H),1.49 (m, 4H), 1.37 (s, 2H) ppm; MS (ES) 452.2 (M+H).

5-amino-N-(4-methylphenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #39), ¹H-NMR (DMSO-d₆, 300 MHz) 9.34 (s, 1H), 8.91 (s, 1H),7.55 (d, J=9.0 Hz, 2H), 7.49 (d, J=8.4 Hz, 2H), 7.27 (s, 2H), 7.15 (d,J=8.4 Hz, 2H), 6.81 (d, J=9.0 Hz, 2H), 3.98 (t, J=6.0 Hz, 2H), 2.61 (t,J=6.0 Hz, 2H), 2.42 (m, 4H), 2.28 (s, 3H), 1.49 (m, 4H) 1.38 (m, 2H)ppm; MS (ES) 452.2 (M+H).

5-amino-N-(4-(methoxy)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #40), ¹H-NMR (DMSO-d₆, 300 MHz) 9.34 (s, 1H), 8.90 (s, 1H),7.56 (d, J=9.0 Hz, 2H), 7.49 (d, J=8.4 Hz, 2H), 7.25 (s, 2H), 6.92 (d,J=8.7 Hz, 2H), 6.80 (d, J=9.0 Hz, 2H), 3.98 (t, J=5.4 Hz, 2H), 3.74 (s,3H) 2.61 (m, 2H), 2.42 (m, 4H), 1.49 (m, 4H), 1.36 (m, 2H) ppm; MS (ES)452.8 (M+H).

5-amino-N-(4-(iso-propyl)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #41), ¹H-NMR (DMSO-d₆, 300 MHz) 9.35 (s, 1H), 8.91 (s, 1H),7.55 (d, J=9.0 Hz, 2H), 7.52 (d, J=9.0 Hz, 2H), 7.28 (s, 2H), 7.22 (d,J=8.1 Hz, 2H), 6.81 (d, J=7.8 Hz, 2H), 3.98 (t, J=6.0 Hz, 2H), 2.61 (t,J=6.0 Hz, 2H), 2.56 (m, 1H), 2.41 (m, 4H), 1.49 (m, 4H), 1.37 (m, 2H),1.20 (d, J=6.3 Hz, 6H) ppm; MS (ES) 464.9 (M+H).

5-amino-N-cyclohexyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #42), ¹H-NMR (DMSO-d₆, 300 MHz) 8.81 (s, 1H), 7.45 (d, J=9.0Hz, 2H), 7.21 (d, J=7.8 Hz, 1H), 7.15 (s, 2H), 6.79 (d, J=9.3 Hz, 2H),3.97 (m, 2H), 3.56 (m, 1H), 2.60 (m, 2H), 2.42 (m, 4H), 1.47 (m, 16H)ppm; MS (ES) 428.7 (M+H).

5-amino-N-(3,4-(dimethoxy)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #43), ¹H-NMR (DMSO-d₆, 300 MHz) 9.30 (s, 1H), 8.90 (s, 1H),7.56 (d, J=8.7 Hz, 2H), 7.285 (d, J=2.1 Hz, 1H), 7.278 (s, 2H), 7.14(dd, J=8.4, 2.1 Hz, 1H), 6.92 (d, J=9.0 Hz, 1H), 6.81 (d, J=9.0 Hz, 2H),3.98 (t, J=5.7 Hz, 2H), 3.75 (s, 3H), 3.74 (s, 3H), 2.60 (t, J=5.7 Hz,2H), 2.43 (m, 4H), 1.49 (m, 4H), 1.37 (s, 2H) ppm; MS (ES) 482.2 (M+H).

5-amino-N-(4-(dimethylamino)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #44), ¹H-NMR (DMSO-d₆, 300 MHz) 9.17 (s, 1H), 8.89 (s, 1H),7.56 (d, J=8.7 Hz, 2H), 7.36 (d, J=8.7 Hz, 2H), 7.22 (s, 2H), 6.81 (d,J=8.7 Hz, 2H), 6.70 (d, J=8.7 Hz, 2H), 4.01 (t, J=6.6 Hz, 2H), 2.86 (s,3H), 2.80 (s, 3H), 2.48 (m, 2H), 1.97 (m, 4H), 1.50-1.14 (m, 6H) ppm; MS(ES) 465.2 (M+H), 463.3 (M−H).

5-amino-N-cyclopentyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #45), ¹H-NMR (DMSO-d₆, 300 MHz) 8.79 (s, 1H), 7.45 (d, J=8.7Hz, 2H), 7.28 (d, J=7.8 Hz, 1H), 7.15 (s, 2H), 6.79 (d, J=9.0 Hz, 2H),3.97 (m, 3H), 2.60 (m, 2H), 2.41 (m, 4H), 1.89-1.38 (m, 14H) ppm; MS(ES) 414.2 (M+H); and

5-amino-N-(4-butoxyphenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide(compound #46), ¹H-NMR (CDCl₃, 300 MHz) 8.37 (s, 1H), 7.39 (d, J=8.7 Hz,2H), 7.32 (d, J=8.7 Hz, 2H), 6.90 (d, J=8.7 Hz, 2H), 6.88 (d, J=8.7 Hz,2H), 6.57 (s, 1H), 6.23 (s, 2H), 4.09 (t, J=6.0 Hz, 2H), 3.96 (t, J=6.3Hz, 2H), 2.77 (t, J=6.0 Hz, 2H), 2.50 (m, 4H), 1.80-1.26 (m, 12H), 0.99(t, J=7.2 Hz, 3H) ppm; MS (ES) 494.8 (M+H).

In addition to the preparation of the compounds of the invention asdisclosed above, the following compounds of the invention were preparedby methods similar to those disclosed herein utilizing appropriatelysubstituted starting materials and reagents. The number following eachcompound below refers to its number in Tables 1-10, as discussed in moredetail below.

-   3-amino-1-(4-(iso-propoxy)phenyl)carbonyl-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole    (compound #47);-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-(4-(morpholin-4-yl)phenylamino]-1H-1,2,4-triazole    (compound #48), yellow solid. ¹H-NMR (DMSO-d₆, 300 MHz) 8.97 (s,    1H), 8.23 (d, J=8.1 Hz, 2H), 7.69 (br. s, 2H), 7.40 (d, J=8.4 Hz,    2H), 7.05 (d, J=8.4 Hz, 2H), 6.84 (d, J=9.0 Hz, 2H), 4.77 (quint.,    J=6.3 Hz, 1H), 3.70 (t, J=4.35 Hz, 4H), 2.98 (t, J=4.65 Hz, 4H),    1.31 (d, J=5.7 Hz, 6H) ppm; MS (ES) 423.10 (M+H), 421.20 (M−H).-   3-amino-1-(4-(iso-propoxy)phenyl)carbonyl-5-(4-(morpholin-4-yl)phenylamino]-1H-1,2,4-triazole    (compound #49);

5-amino-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1-(4-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole(compound #50), yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.02 (s, 1H),8.19 (d, J=9.0 Hz, 2H), 7.72 (br. s, 2H), 7.40 (d, J=7.5 Hz, 2H), 7.12(d, J=8.7 Hz, 2H), 6.80 (d, J=8.1 Hz, 2H), 3.96 (t, J=5.7 Hz, 2H), 2.59(t, J=5.7 Hz, 2H), 2.39 (m, 4H), 1.47 (m, 4H), 1.41 (s, 9H), 1.37-1.34(m, 2H) ppm; MS (ES) 479.92 (M+H), 477.58 (M−H).

5-amino-1-(4-(iso-propyl)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #51), yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (s, 1H),8.12 (d, J=8.4 Hz, 2H), 7.74 (br. s, 2H), 7.43-7.38 (m, 4H), 6.81 (d,J=9 Hz, 2H), 3.98 (t, J=5.85 Hz, 2H), 2.99 (quint., J=7 Hz, 1H), 2.66(m, 2H), 2.55-2.4 (m, 4H), 1.56-1.45 (m, 4H), 1.40-1.35 (m, 2H), 1.25(d, J=6.9 Hz, 6H) ppm; MS (ES) 449.50 (M+H), 447.48 (M−H).

5-amino-1-(4-(iso-propyl)phenyl)carbonyl-3-(4-(morpholin-4-yl)phenylamino]-1H-1,2,4-triazole(compound #52), yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 8.97 (s, 1H),8.13 (d, J=8.4 Hz, 2H), 7.73 (br. s, 2H), 7.41 (d, J=8.7 Hz, 2H), 7.38(d, J=9.0 Hz, 2H), 6.82 (d, J=9.3 Hz, 2H), 3.70 (m, 4H), 2.97 (m, 5H),1.25 (d, J=6.9 Hz, 6H) ppm; MS (ES) 407.14 (M+H), 405.24 (M−H).

5-amino-1-(4-(methyl)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #53), yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (s, 1H),8.09 (d, J=8.4 Hz, 2H), 7.73 (br. s, 2H), 7.41-7.33 (m, 4H), 6.80 (d,J=8.7 Hz, 2H), 3.99 (m, 2H), 2.52 (m, 2H), 2.41 (s, 4H), 1.82 (s, 3H),1.50 (br. s, 4H), 1.39 (br. s, 2H) ppm; MS (ES) 421.47 (M+H), 419.42(M−H).

5-amino-1-(4-(methyl)phenyl)carbonyl-3-(4-(morpholin-4-yl)phenylamino)-1H-1,2,4-triazole(compound #54), yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 8.98 (s, 1H),8.10 (d, J=8.1 Hz, 2H), 7.72 (br. s, 2H), 7.38 (d, J=8.7 Hz, 2H), 7.35(d, J=8.7 Hz, 2H), 6.82 (d, J=8.7 Hz, 2H), 3.70 (m, 4H), 2.97 (m, 4H),2.41 (s, 3H) ppm; MS (ES) 379.13 (M+H), 377.16 (M−H).

5-amino-3-[4-(iso-propoxy)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole(compound #55), yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.01 (s, 1H),8.09 (d, J=8.4 Hz, 2H), 7.73 (br. s, 2H), 7.38 (d, J=9.3 Hz, 2H), 7.35(d, J=8.4 Hz, 2H), 6.77 (d, J=8.7 Hz, 2H), 4.45 (quint., J=5.9 Hz, 1H),2.40 (s, 3H), 1.20 (d, J=6.0 Hz, 6H) ppm; MS (ES) 352.11 (M+H), 350.19(M−H).

-   3-amino-5-[4-(iso-propoxy)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #56);

5-amino-3-(4-(morpholin-4-yl)phenylamino)-1-(4-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole(compound #57); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 8.97 (s, 1H),8.17 (d, J=9 Hz, 2H), 7.71 (br. s, 2H), 7.38 (d, J=9 Hz, 2H), 7.11 (d,J=8.7 Hz, 2H), 6.82 (d, J=9.0 Hz, 2H), 3.70 (m, 4H), 2.97 (m, 4H), 1.41(s, 9H) ppm; MS (ES) 437.17 (M+H), 435.26 (M−H).

-   3-amino-5-(4-(morpholin-4-yl)phenylamino)-1-(4-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #58);

5-amino-1-(3-(methyl)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #59); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.04 (s, 1H),8.15 (s, 1H), 8.02 (br. s, 1H), 7.90 (d, J=6 Hz, 1H), 7.74 (br. s, 2H),7.44-7.38 (m, 4H), 6.78 (d, J=9.3 Hz, 2H), 3.96 (t, J=5.85 Hz, 2H), 2.59(t, J=6 Hz, 2H), 2.42 (m, 4H), 2.41 (s, 3H), 1.48 (m, 4H), 1.37 (m, 2H)ppm; MS (ES) 421.47 (M+H), 419.44 (M−H).

5-amino-1-(4-(iso-propoxy)phenylcarbonyl-3-[4-[2-(thiomorpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #60); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.02 (s, 1H),8.23 (d, J=9.0 Hz, 2H), 7.70 (br. s, 2H), 7.41 (d, J=9.0 Hz, 2H), 7.05(d, J=9.0 Hz, 2H), 6.82 (d, J=9.0 Hz, 2H), 4.78 (quint., J=5.9 Hz, 1H),3.97 (t, J=6.0 Hz, 2H), 2.74-2.67 (m, 6H), 2.59-2.56 (m, 4H), 1.31 (d,J=5.7 Hz, 6H) ppm; MS (ES) 483.47 (M+H), 481.36 (M−H).

5-amino-1-(3-(methyl)phenylcarbonyl-3-[4-[2-(thiomorpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #61); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (s, 1H),8.02 (br. s, 1H), 7.90 (d, J=6.3 Hz, 1H), 7.73 (br. s, 2H), 7.44-7.39(m, 4H), 6.78 (d, J=8.7 Hz, 2H), 3.96 (t, J=5.8 Hz, 2H), 2.74-2.71 (m,4H), 2.68 (t, J=5.7 Hz, 2H), 2.59-2.56 (m, 4H), 2.41 (s, 3H) ppm; MS(ES) 439.41 (M+H), 437.33 (M−H).

-   5-amino-1-(4-(cyclohexyl)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole    (compound #62);-   5-amino-3-(2,2-difluoro-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)amino-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #63);-   5-amino-3-(2,2-difluoro-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)amino-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #64);

5-amino-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-3-(4-(iso-propoxy)phenyl)amino-1H-1,2,4-triazole(compound #65); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 10.87 (s, 1H),9.02 (s, 1H), 7.94 (dd, J=8.1 Hz, J=1.8 Hz, 1H), 7.72 (br. s, 2H), 7.69(d, J=1.8 Hz, 1H), 7.39 (d, J=9.0 Hz, 2H), 7.08 (d, J=8.4 Hz, 1H), 6.77(d, J=9.0 Hz, 2H), 4.45 (quint., J=6.0 Hz, 1H), 1.46 (s, 6H), 1.21 (d,J=6.0 Hz, 6H) ppm; MS (ES) 437.46 (M+H), 435.38 (M−H).

-   3-amino-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-5-(4-(iso-propoxy)phenyl)amino-1H-1,2,4-triazole    (compound #66);

5-amino-1-(3-(hydroxy)phenyl)carbonyl-3-(4-(morpholin-4-yl)phenylamino)-1H-1,2,4-triazole(compound #67); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.77 (s, 1H),8.97 (s, 1H), 7.72 (br. s, 2H), 7.59 (d, J=7.8 Hz, 1H), 7.49 (t, J=1.95Hz, 1H), 7.38 (d, J=8.7 Hz, 2H), 7.32 (t, J=7.8 Hz, 1H), 7.00 (dd, J=7.8Hz, J=1.8 Hz, 1H), 6.80 (d, J=9.0 Hz, 2H), 3.70 (m, 4H), 2.96 (m, 4H)ppm; MS (ES) 381.08 (M+H), 379.16 (M−H).

5-amino-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-3-(4-(morpholin-4-yl)phenylamino)-1H-1,2,4-triazole(compound #68); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 10.86 (s, 1H),8.96 (s, 1H), 7.98 (dd, J=8.4 Hz, J=2.1 Hz, 1H), 7.70 (br. s, 2H), 7.66(d, J=2.1 Hz, 1H), 7.38 (d, J=9.0 Hz, 2H), 7.08 (d, J=8.4 Hz, 1H), 6.82(d, J=9.0 Hz, 2H), 3.70 (m, 4H), 2.97 (m, 4H), 1.45 (s, 6H) ppm; MS (ES)464.46 (M+H), 462.41 (M−H).

-   3-amino-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-5-(4-(morpholin-4-yl)phenylamino)-1H-1,2,4-triazole    (compound #69);-   5-amino-1-(4-(aminosulfonyl)phenyl)carbonyl-3-(4-(morpholin-4-yl)phenylamino)-1H-1,2,4-triazole    (compound #70);

5-amino-3-[4-(iso-propoxy)phenylamino]-1-(3-(nitro)phenyl)carbonyl-1H-1,2,4-triazole(compound #71); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.25 (t, J=2.1Hz, 1H), 9.12 (s, 1H), 8.49-8.45 (m, 2H), 7.87-7.81 (m, 3H), 7.42 (d,J=8.7 Hz, 2H), 6.76 (d, J=9.0 Hz, 2H), 4.43 (quint., J=6.0 Hz, 1H), 1.21(d, J=6.0 Hz, 6H) ppm; MS (ES) 383.39 (M+H), 381.36 (M−H).

5-amino-3-(4-(morpholin-4-yl)phenylamino)-1-(3-(nitro)phenyl)carbonyl-1H-1,2,4-triazole(compound #72); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.22 (s, 1H),9.08 (s, 1H), 8.48 (m, 2H), 7.84 (m, 3H), 7.40 (d, J=8.1 Hz, 2H), 6.80(d, J=8.7 Hz, 2H), 3.70 (m, 4H), 2.96 (m, 4H) ppm; MS (ES) 410.42 (M+H),408.38 (M−H).

5-amino-1-(3-(hydroxy)phenyl)carbonyl-3-[4-(iso-propoxy)phenylamino]-1H-1,2,4-triazole(compound #73); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.74 (s, 1H),8.99 (s, 1H), 7.71 (br. s, 2H), 7.58 (d, J=8.1 Hz, 1H), 7.50 (t, J=2.4Hz, 1H), 7.38 (d, J=9.3 Hz, 2H), 7.32 (t, J=7.9 Hz, 1H), 6.99 (dd, J=8.1Hz, J=2.7 Hz, 1H), 6.74 (d, J=9.3 Hz, 2H), 4.44 (quint., J=6.0 Hz, 1H),1.20 (d, J=5.7 Hz, 6H) ppm; MS (ES) 354.41 (M+H), 352.38 (M−H).

5-amino-1-(3-(chloro)phenyl)carbonyl-3-(4-(morpholin-4-yl)phenylamino)-1H-1,2,4-triazole(compound #74); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (s, 1H),8.29 (t, J=1.8 Hz, 1H), 8.02 (d, J=7.8 Hz, 1H), 7.77 (br. s, 2H),7.72-7.69 (m, 1H), 7.57 (t, J=7.95 Hz, 1H), 7.37 (d, J=9.3 Hz, 2H), 6.80(d, J=9.3 Hz, 2H), 3.70 (m, 4H), 2.96 (m, 4H) ppm; MS (ES) 399.38 (M+H),397.34 (M−H).

-   3-amino-1-(3-(chloro)phenyl)carbonyl-5-(4-(morpholin-4-yl)phenylamino)-1H-1,2,4-triazole    (compound #75);-   5-amino-1-(3-(chloro)phenyl)carbonyl-3-[4-(iso-propoxy)phenylamino]-1H-1,2,4-triazole    (compound #76);

5-amino-3-[4-(iso-propoxy)phenylamino]-1-[4-[2-(piperidin-1-yl)ethoxy]phenyl)carbonyl-1H-1,2,4-triazole(compound #77); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.01 (s, 1H),8.24 (d, J=9.0 Hz, 2H), 7.70 (br. s, 2H), 7.40 (d, J=9.0 Hz, 2H), 7.08(d, J=9.3 Hz, 2H), 6.80 (d, J=9.0 Hz, 2H), 4.45 (quint., J=6.0 Hz, 1H),4.18 (t, J=5.7 Hz, 2H), 2.70 (t, J=5.7 Hz, 2H), 2.60 (m, 4H), 1.56-1.47(m, 4H), 1.38 (m, 2H), 1.21 (d, J=6.0 Hz, 6H) ppm; MS (ES) 465.59 (M+H),463.55 (M−H).

5-amino-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #78); yellow solid, 1H-NMR (DMSO-d₆, 300 MHz) 10.86 (s, 1H),9.02 (s, 1H), 7.96 (dd, J=8.4 Hz, J=1.8 Hz, 1H), 7.71 (br. s, 2H), 7.67(d, J=1.8 Hz, 1H), 7.40 (d, J=8.7 Hz, 2H), 7.08 (d, J=8.1 Hz, 1H), 6.79(d, J=8.4 Hz, 2H), 3.97 (t, J=5.85 Hz, 2H), 2.62 (t, J=5.7 Hz, 2H), 2.43(m, 4H), 1.54-1.44 (m, 4H), 1.45 (s, 6H), 1.42-1.32 (m, 2H) ppm; MS (ES)506.14 (M+H), 504.33 (M−H).

5-amino-1-(3-(methoxycarbonyl)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #79); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.09 (s, 1H),8.90 (t, J=1.2 Hz, 1H), 8.34 (dt, J=7.8 Hz, J=1.8 Hz, 1H), 8.19 (dt,J=7.5 Hz, J=1.5 Hz, 1H), 7.80 (br. s, 2H), 7.70 (t, J=7.5 Hz, 1H), 7.41(d, J=9.0 Hz, 2H), 6.77 (d, J=9.0 Hz, 2H), 3.96 (t, J=6.0 Hz, 2H), 3.89(s, 3H), 2.59 (t, J=6.0 Hz, 2H), 2.39 (m, 4H), 1.49-1.22 (m, 6H) ppm; MS(ES) 465.95 (M+H), 463.52 (M−H).

5-amino-1-(3-(methoxy)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #80); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.05 (s, 1H),7.77 (br. s, 2H), 7.70-7.66 (m 2H), 7.46 (d, J=7.8 Hz, 1H), 7.40 (d,J=8.7 Hz, 2H), 7.19 (dd, J=8.4 Hz, J=3.0 Hz, 1H), 6.77 (d, J=9.0 Hz,2H), 3.95 (t, J=5.85 Hz, 2H), 3.82 (s, 3H), 2.58 (t, J=6 Hz, 2H), 2.39(m, 4H), 1.46 (m, 4H), 1.37 (m, 2H) ppm; MS (ES) 437.89 (M+H), 435.53(M−H).

5-amino-1-(3-(methoxy)phenyl)carbonyl-3-(4-(morpholin-4-yl)phenylamino)-1H-1,2,4-triazole(compound #81); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.01 (s, 1H),7.78 (t, J=1.9 Hz, 1H), 7.75 (br. s, 2H), 7.69 (d, J=7.8 Hz, 1H), 7.45(t, J=8.1 Hz, 1H), 7.39 (d, J=9.0 Hz, 2H), 7.19 (dd, J=8.1 Hz, J=2.4 Hz,1H), 6.79 (d, J=9.0 Hz, 2H), 3.82 (s, 3H), 3.70 (m, 4H), 2.97 (m, 4H)ppm; MS (ES) 395.09 (M+H), 393.22 (M−H).

-   5-amino-3-[4-[2-(dimethylamino)ethoxy]phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #82);

5-amino-3-[4-[2-(dimethylamino)ethoxy]phenylamino]-1-(4-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole(compound #83); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.02 (s, 1H),8.17 (d, J=8.7 Hz, 2H), 7.71 (br. s, 2H), 7.41 (d, J=9.0 Hz, 2H), 7.11(d, J=8.7 Hz, 2H), 6.81 (d, J=9.0 Hz, 2H), 3.98 (t, J=5.85 Hz, 2H), 2.68(t, J=5.85 Hz, 2H), 2.27 (s, 6H), 1.41 (s, 9H) ppm; MS (ES) 439.61(M+H), 437.61 (M−H).

5-amino-3-[4-[2-(dimethylamino)propoxy]phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole(compound #84); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.02 (s, 1H),8.23 (d, J=9.0 Hz, 2H), 7.70 (br. s, 2H), 7.42 (d, J=9.0 Hz, 2H), 7.05(d, J=9.3 Hz, 2H), 6.01 (d, J=9.0 Hz, 2H), 4.78 (quint., J=6.0 Hz, 1H),3.91 (t, J=6.1 Hz, 2H), 2.53 (m, 2H), 2.28 (s, 6H), 1.85 (quint., J=6.9Hz, 2H), 1.31 (d, J=5.7 Hz, 6H) ppm; MS (ES) 439.61 (M+H), 437.64 (M−H).

5-amino-3-[4-[2-(dimethylamino)ethoxy]phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole(compound #85); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (s, 1H),8.23 (d, J=9.0 Hz, 2H), 7.70 (br. s, 2H), 7.42 (d, J=9.0 Hz, 2H), 7.05(d, J=9.3 Hz, 2H), 6.83 (d, J=9.0 Hz, 2H), 4.78 (quint., J=6.0 Hz, 1H),3.97 (t, J=5.85 Hz, 2H), 2.65 (t, J=5.7 Hz, 2H), 2.24 (s, 6H), 1.31 (d,J=6.0 Hz, 6H) ppm; MS (ES) 425.18 (M+H), 423.23 (M−H).

5-amino-3-[4-[2-(dimethylamino)ethoxy]phenylamino]-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-1H-1,2,4-triazole(compound #86); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 10.87 (s, 1H),9.03 (s, 1H), 7.95 (dd, J=8.4 Hz, J=2.1 Hz, 1H), 7.72 (br. s, 2H), 7.68(d, J=2.1 Hz, 1H), 7.40 (dd, J=6.9 Hz, J=2.4 Hz, 2H), 7.08 (d, J=8.4 Hz,1H), 6.80 (d, J=9.3 Hz, 2H), 3.95 (t, J=5.85 Hz, 2H), 2.60 (t, J=5.7 Hz,2H), 2.21 (s, 6H), 1.45 (s, 6H) ppm; MS (ES) 466.15 (M+H), 464.22 (M−H).

5-amino-3-[4-[2-(dimethylamino)ethoxy]phenylamino]-1-(4-(dimethylamino)phenyl)carbonyl-1H-1,2,4-triazole(compound #87); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 8.97 (s, 1H),8.24 (d, J=9.3 Hz, 2H), 7.63 (br. s, 2H), 7.44 (d, J=9.0 Hz, 2H), 6.84(d, J=9.0 Hz, 2H), 6.76 (d, J=9.6 Hz, 2H), 3.96 (t, J=5.85 Hz, 2H), 3.04(s, 6H), 2.58 (t, J=6 Hz, 2H), 2.20 (s, 6H) ppm; MS (ES) 410.18 (M+H),408.22 (M−H).

5-amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[4-[2-(dimethylamino)propoxy]phenylamino]-1H-1,2,4-triazole(compound #88); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 8.97 (s, 1H),8.25 (d, J=9.3 Hz, 2H), 7.63 (br. s, 2H), 7.44 (d, J=9.0 Hz, 2H), 6.82(d, J=9.0 Hz, 2H), 6.77 (d, J=9.6 Hz, 2H), 3.19 (t, J=6.3 Hz, 2H), 3.04(s, 6H), 2.39 (t, J=5.4 Hz, 2H), 2.17 (d, J=1.5 Hz, 6H), 1.81 (Quint.,J=6.75 Hz, 2H) ppm; MS (ES) 424.19 (M+H), 422.29 (M−H).

5-amino-3-[4-[2-(dimethylamino)propoxy]phenylamino]-1-(4-(tert-butoxy)phenyl)carbonyl-1H-1,2,4-triazole(compound #89); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.01 (s, 1H),8.17 (d, J=8.7 Hz, 2H), 7.71 (br. s, 2H), 7.40 (d, J=9.0 Hz, 2H), 7.11(d, J=8.7 Hz, 2H), 6.78 (d, J=8.7 Hz, 2H), 3.89 (t, J=6.3 Hz, 2H), 2.31(t, J=6.9 Hz, 2H), 2.11 (s, 6H) 1.78 (m, 2H), 1.41 (s, 9H) ppm; MS (ES)453.19 (M+H), 451.33 (M−H).

5-amino-3-[4-[2-(dimethylamino)propoxy]phenylamino]-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-1H-1,2,4-triazole(compound #90); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 10.87 (s, 1H),9.02 (s, 1H), 7.95 (dd, J=9.0 Hz, J=2.1 Hz, 1H), 7.72 (br. s, 2H), 7.68(d, J=1.8 Hz, 1H), 7.40 (d, J=9.0 Hz, 2H), 7.08 (d, J=8.4 Hz, 1H), 6.78(d, J=9.3 Hz, 2H), 3.89 (t, J=6.4 Hz, 2H), 2.31 (t, J=7.0 Hz, 2H), 2.11(s, 6H) 1.78 (m, 2H), 1.45 (s, 9H) ppm; MS (ES) 480.14 (M+H), 478.31(M−H).

5-amino-3-[4-[3-(dimethylamino)propoxy]phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole(compound #91); yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.02 (s, 1H),8.09 (d, J=8.4 Hz, 2H), 7.73 (br. s, 2H), 7.39 (d, J=9.3 Hz, 2H), 7.35(d, J=8.7 Hz, 2H), 6.78 (d, J=9.0 Hz, 2H), 3.89 (t, J=6.4 Hz, 2H), 2.40(s, 3H), 2.32 (t, J=7.2 Hz, 2H), 2.12 (s, 6H) 1.78 (quint., J=6.9 Hz,2H) ppm; MS (ES) 395.16 (M+H), 393.28 (M−H).

-   3-amino-5-(1,4-benzodioxan-6-yl)amino-1-phenylcarbonyl-1H-1,2,4-triazole    (compound #92);-   3-amino-5-(1,4-benzodioxan-6-yl)amino-1-methoxycarbonyl-1H-1,2,4-triazole    (compound #93);-   5-amino-1-(2-(chloro)phenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #94);-   5-amino-1-(4-(chloro)phenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #95);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #96);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(2-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #97);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(3-(methoxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #98);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(2-(fluoro)phenyl)carbonyl-1H-1,2,4-triazole    (compound #99);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(4-(fluoro)phenyl)carbonyl-1H-1,2,4-triazole    (compound #100);-   5-amino-1-(3-(chloro)phenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #101);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(4-(methyloxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #102);-   5-amino-3-(2-(ethoxycarbonyl)benzofuran-5-yl)amino-1-(3-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #103);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #104);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(3-(fluoro)phenyl)carbonyl-1H-1,2,4-triazole    (compound #105);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(2-(methyloxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #106);-   5-amino-3-[3-(hydroxy)phenylamino]-1-(2-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #107, (Ia-6));-   5-amino-3-[3-(hydroxy)phenylamino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #108, (Ia-7));-   1-(4-(Acetoxy)phenyl)carbonyl-5-amino-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #109);-   1-(3-(Acetoxy)phenyl)carbonyl-5-amino-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #110);-   5-amino-3-[4-(iso-propoxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #111);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(3-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #112);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #113);-   5-amino-1-(4-(ethoxyphenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #114);-   5-amino-3-[3-(cyclopentoxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #116);-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-(methoxy)phenylamino]-1H-1,2,4-triazole    (compound #117);-   5-amino-3-[4-(ethoxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #118);-   1-(2-(acetoxy)phenyl)carbonyl-5-amino-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #119);-   5-amino-1-(4-(cyclopentoxy)phenylcarbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #120);-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[3-(methoxy)phenylamino]-1H-1,2,4-triazole    (compound #121);-   5-amino-3-[3-(iso-propoxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #122);-   5-amino-3-[4-(fluoro)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #123);-   5-amino-3-[3-(fluoro)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #124);-   5-amino-3-[3-(ethoxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #125);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-[4-(methoxycarbonylmethoxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #126);-   5-amino-1-(3-(cyclopentoxy)phenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #127);-   5-amino-1-(3-(ethoxy)phenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #128);-   5-amino-3-[2-(fluoro)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #129);-   5-amino-3-[N-(2-(tetrahydropyran-2-yloxy)methylbenzofuran-5-yl)-amino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #130);-   5-amino-3-[4-(methyl)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #131);-   5-amino-3-[4-(methoxy)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #132);-   5-amino-3-[3-(methyl)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #133);-   5-amino-3-[3-(methoxy)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #134);-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[3-(methoxycarbonylmethoxy)phenylamino]-1H-1,2,4-triazole    (compound #135);-   5-amino-3-(2-(hydroxymethyl)benzofuran-5-yl)amino-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #136);-   5-amino-1-(4-(methyl)phenyl)carbonyl-3-phenylamino-1H-1,2,4-triazole    (compound #137);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-[3-(methoxycarbonylmethoxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #138);-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[3-(2,2,2-trifluoroethoxy)phenylamino]-1H-1,2,4-triazole    (compound #139);

3-amino-5-phenylamino-1-(trans-2-(furan-2-yl)ethenyl)carbonyl-1H-1,2,4-triazole(compound #140); mp 190-193° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 10.04 (s,1H), 7.94 (s, 1H), 7.76-7.66 (m, 3H), 7.39-7.30 (m, 3H), 7.10 (m, 2H),6.71 (m, 2H), 6.15 (br s, 2H); ¹³C NMR (75 MHz, DMSO-d₆) δ 163.5, 160.9,152.7, 150.1, 146.2, 137.5, 131.5, 128.4, 122.4, 118.2, 117.3, 113.5,112.6; IR (ATR) 3193, 1598, 1527 cm⁻¹; ESI MS m/z 296 [C₁₆H₁₃N₆O₂+H]⁺;HPLC (Method 1)>99% (AUC), t_(R)=14.22 min.

5-amino-3-phenylamino-1-(trans-2-(furan-2-yl)ethenyl)carbonyl-1H-1,2,4-triazole(compound #141); mp 212-216° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.30 (s,1H), 7.97 (s, 1H), 7.72-7.57 (m, 5H), 7.34-7.25 (m, 3H), 7.11 (d, J=3.3Hz, 1H), 6.88 (m, 1H), 6.71 (m, 1H); ¹³C NMR (75 MHz, DMSO-d₆) δ 162.2,156.6, 154.9, 149.1, 145.2, 139.5, 130.5, 127.2, 118.6, 116.3, 115.2,112.3, 111.6; IR (ATR) 3334, 1674, 1642, 1609 cm⁻¹; ESI MS m/z 296[C₁₆H₁₃N₅O₂+H]⁺; HPLC (Method 1)>99% (AUC), t_(R)=13.38 min.

-   5-amino-1-(4-(benzyloxy)phenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #142);-   5-amino-3-[2-(methoxy)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #143);-   5-amino-3-[2-(methyl)phenylamino]-1-(4-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #144);-   5-amino-3-[-[2-(hydroxyl)ethoxy]phenylamino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #145);-   5-amino-3-[3-(methylaminocarbonylmethoxy)phenylamino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #146);-   5-amino-3-[3-(methoxycarbonylmethoxy)phenylamino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #147);-   5-amino-3-[3-(N-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl)aminocarbonylmethoxy)phenylamino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #148);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-[4-[2-(morpholin-4-yl)ethoxy]phenyl]carbonyl-1H-1,2,4-triazole    (compound #149);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-[3-[2-(morpholin-4-yl)ethoxy]phenyl]carbonyl-1H-1,2,4-triazole    (compound #150);-   5-amino-3-[4-(cyclopentoxy)phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #151);-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-(2,2,2-trifluoroethoxy)phenylamino]-1H-1,2,4-triazole    (compound #152);-   5-amino-3-[3-(N-(2,3-dihydroxypropyl)amino)carbonylmethoxy]-phenylamino-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #153);-   5-amino-3-(indazol-5-yl)amino-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #154);-   3-amino-1-(3-(benzyloxy)phenyl)carbonyl-5-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #155);-   5-amino-1-(3-(benzyloxy)phenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #156);-   5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-(methoxycarbonylmethoxy)phenylamino]-1H-1,2,4-triazole    (compound #157);-   5-amino-3-[4-[2-(1,3-dioxolan-2-yl)ethoxy]phenylamino]-1-(4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #158);-   5-amino-1-(4-(iso-propoxy)phenylcarbonyl-3-[4-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole    (compound #159);-   5-amino-3-(indazol-6-yl)amino-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #160);-   5-amino-3-(benzo[b][1,4]oxazin-3(4H)-on-6-yl)amino-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #161);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(4-(hydroxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #162);-   5-amino-1-(4-(iso-propoxy)phenylcarbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole    (compound #163);-   3-amino-5-[3-[cyclohexylaminocarbonylmethoxy]phenylamino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #164);-   5-amino-3-[3-[cyclohexylaminocarbonylmethoxy]phenylamino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #165);-   5-amino-3-(1,4-benzodioxan-6-yl)-amino-1-(3-(hydroxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #166);-   3-amino-5-[(2H,3H-4-tert-butoxycarbonylbenzo[1,4]oxazin-6-yl)-[(2H,3H-4-tert-butoxycarbonylbenzo[1,4]oxazin-6-yl)amino]-1-(3-(methyl)phenyl)carbonyl-1H-1,2,4-triazole    (compound #167);

5-amino-1-(3-(iso-propoxy)phenyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #168); off-white solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.05 (s,1H), 8.14 (d, J=0.9 Hz, 1H), 7.74 (d, J=8.4 Hz, 2H), 7.63 (d, J=7.4 Hz,1H), 7.43 (t, J=7.7 Hz, 1H), 7.40 (d, J=8.7 Hz, 2H), 7.17 (dd, J=8.3 Hz,J=2.6 Hz, 1H), 6.76 (d, J=8.7 Hz, 2H), 4.66 (quint, J=6.0 Hz, 1H), 3.97,(t, J=5.9 Hz, 2H), 2.62 (t, J=6.0 Hz, 2H), 2.42 (m, 4H), 1.48 (m, 4H),1.38-1.35 (m, 2H), 1.29 (d, J=6 Hz, 6H) ppm; MS (ES) 465.57 (M+H),453.55 (M−H).

5-amino-1-(3-(iso-propoxy)phenyl)carbonyl-3-[4-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #169); off-white solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.05 (s,1H), 8.12 (d, J=1.5 Hz, 1H), 7.74 (d, J=9.3 Hz, 2H), 7.63 (d, J=7.5 Hz,1H), 7.46-7.36 (m, 3H), 7.17 (d, J=7.5 Hz, 1H), 6.77 (d, J=8.7 Hz, 2H),4.66 (quint., J=5.1 Hz, 1H), 3.98 (t, J=5.9 Hz, 1H), 3.55 (t, J=4.5 Hz,2H), 2.63 (t, J=5.6 Hz, 1H), 2.44 (m, 2H), 1.29 (d, J=5.1 Hz, 6H) ppm;MS (ES) 467.14 (M+H), 465.30 (M−H).

5-amino-1-(3-(iso-propoxy)phenyl)carbonyl-3-[3-(1,3-oxazol-5-yl)phenylamino]-1H-1,2,4-triazole(compound #170); white solid, ¹H-NMR (MeOH-d₄, 300 MHz) 8.18 (s, 1H),8.13 (m, 1H), 7.78-7.72 (m, 2H), 7.44 (t, J=8.1 Hz, 1H), 7.33-7.19 (m,5H), 4.63 (quint., J=5.7 Hz, 1H), 1.26 (d, J=5.7 Hz, 6H) ppm; MS (ES)405.06 (M+H), 403.15 (M−H).

5-amino-1-(3-(iso-propoxy)pyridin-5-yl)carbonyl-3-[4-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #171), yellow solid, ¹H-NMR (DMSO-d₆, 300 MHz) 9.09 (s, 1H),8.74 (d, J=1.8 Hz, 1H), 8.44 (d, J=2.7 Hz, 1H), 8.05 (t, J=1.5 Hz, 1H),7.79 (br. s, 2H), 7.37 (d, J=8.7 Hz, 2H), 6.76 (d, J=9 Hz, 2H), 4.73(quint., J=6 Hz, 1H), 3.98 (t, J=5.4 Hz, 2H), 3.55 (m, 4H), 2.63 (t,J=5.7 Hz, 2H), 2.43 (m, 4H), 1.31 (d, J=6 Hz, 6H) ppm; MS (ES) 468.48(M+H), 466.49 (M−H).

-   5-amino-N-(4-chlorophenyl)-3-[4-(methoxy)phenylamino]-1H-1,2,4-triazole-1-carboxamide    (compound #172);-   5-amino-3-(4-methoxyphenyl)amino-1-(tert-butoxycarbonyl)-1H-1,2,4-triazole    (compound #173);-   3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-(4-chlorophenyl)-1H-1,2,4-triazole-1-carboxamide    (compound #174);-   3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-(1,3-benzodioxol-5-yl)-1H-1,2,4-triazole-1-carboxamide    (compound #175);-   5-[4-(acetyl(methyl)amino)phenyl]amino-3-amino-N-(1,3-benzodioxol-5-yl)-1H-1,2,4-triazole-1-carboxamide    (compound #176);-   3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-cyclopentyl-1H-1,2,4-triazole-1-carboxamide    (compound #177);-   5-[4-(acetyl(methyl)amino)phenyl]amino-3-amino-N-cyclopentyl-1H-1,2,4-triazole-1-carboxamide    (compound #178);-   3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-(4-(iso-propyl)phenyl)-1H-1,2,4-triazole-1-carboxamide    (compound #179);-   3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-(4-(butoxy)phenyl)-1H-1,2,4-triazole-1-carboxamide    (compound #180);-   3-amino-N-(4-(butoxy)phenyl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide    (compound #182);-   3-amino-N-(4-(methyl)phenyl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide    (compound #183);-   3-amino-N-(4-(methoxy)phenyl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide    (compound #184);-   3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-cyclohexyl-1H-1,2,4-triazole-1-carboxamide    (compound #185);-   3-[4-(acetyl(methyl)amino)phenyl]amino-3-amino-N-cyclohexyl-1H-1,2,4-triazole-1-carboxamide    (compound #186);-   3-amino-N-(3-(methyl)phenyl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide    (compound #187);-   3-amino-N-(3,5-dimethoxyphenyl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide    (compound #188);-   3-amino-N-cyclohexyl-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide    (compound #189);-   3-amino-N-cyclopentyl-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide    (compound #190);-   3-amino-1-(4-iso-propoxyphenyl)carbonyl-5-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole    (compound #191);-   3-amino-1-(4-(iso-propoxy)phenyl)carbonyl-5-[4-(piperidin-1-yl)phenylamino]-1H-1,2,4-triazole    (compound #192);-   3-amino-N-(1,3-benzodioxol-5-yl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide    (compound #193);-   5-amino-N-(4-cyanophenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide    (compound #194);-   5-amino-1-[2-(bicyclo[2.2.1]hept-5-ene)carbonyl]-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole    (compound #196);-   5-amino-1-(3-(dimethylamino)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole    (compound #197);-   5-amino-1-(3,4-(dimethoxy)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole    (compound #198);-   5-amino-N-(3,5-(dimethyl)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide    (compound #199);-   5-amino-1-[2-(bicyclo[2.2.1]heptane)carbonyl]-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole    (compound #200);-   5-amino-3-[4-(piperidin-1-yl)phenylamino]-1-(tert-butoxycarbonyl)-1H-1,2,4-triazole    (compound #201);-   3-amino-1-(1H-indol-5-yl)carbonyl-5-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole    (compound #202);-   5-amino-1-(pyridin-2-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole    (compound #203);-   5-amino-1-(pyridin-4-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole    (compound #204);-   5-amino-3-[(2H,3H-4-tert-butoxycarbonylbenzo[1,4]oxazin-6-yl)amino]-1-(3-methylphenyl)carbonyl-1,2,4-triazole    (compound #206);-   5-amino-1-(3-methylphenyl)carbonyl-3-[2-[N-[2-(tetrahydropyran-2-yloxy)ethyl]amino]carbonylbenzofuran-5-yl]amino-1H-1,2,4-triazole    (compound #207);-   5-amino-3-[2-[2-hydroxyethylaminocarbonyl]benzofuran-5-yl]amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #208);-   3-amino-1-[3-[2-(1,3-dioxolan-2-yl)ethoxy]phenylcarbonyl-5-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #209);-   5-amino-1-[3-[2-(1,3-dioxolan-2-yl)ethoxy]phenylcarbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #210);-   5-amino-3-[2-(hydroxyl)phenylamino]-1-(4-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #211);-   5-amino-1-(3-methylphenyl)carbonyl-3-[3-[(2-methoxyethoxy)methoxy]phenylamino]-1H-1,2,4-triazole    (compound #212);-   3-amino-1-[4-[2-(1,3-dioxolan-2-yl)ethoxy]phenylcarbonyl-5-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #213);-   5-amino-1-[4-[2-(1,3-dioxolan-2-yl)ethoxy]phenylcarbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #214);-   5-amino-3-[(3,4-dihydrobenzo[1,4]oxazin-6-yl)amino]-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #215);-   5-amino-3-(3-methoxymethoxy)phenylamino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #216);-   5-amino-3-(4-chlorophenyl)amino-1-(4-chlorophenyl)carbonyl-1H-1,2,4-triazole    (compound #217);-   5-amino-3-(4-bromophenyl)amino-1-(4-chlorophenyl)carbonyl-1H-1,2,4-triazole    (compound #218);-   5-amino-3-[2-(ethoxycarbonyl)benzofuran-5-yl]amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #219);-   5-amino-1-(3-methylphenyl)carbonyl-3-(pyridin-3-yl)amino-1H-1,2,4-triazole    (compound #220);-   5-amino-1-(3-methylphenyl)carbonyl-3-[(3-tert-butoxycarbonylmethoxy)phenyl]amino-1H-1,2,4-triazole    (compound #221);-   5-amino-3-(2-methyl-2H-indazol-5yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #222);-   5-amino-1-(3-methylphenyl)carbonyl-3-[3-[2-(tetrahydropyran-2-yl)ethoxyaminocarbonyl]methoxy]phenylamino-1H-1,2,4-triazole    (compound #223);-   5-amino-3-(3-hydroxycarbonylmethoxy)phenylamino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #224);-   5-amino-3-[3-((2-hydroxyethyl)aminocarbonylmethoxy)phenyl]amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #225);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-[4-[2-(piperidin-1-yl)ethoxy]phenylcarbonyl-1H-1,2,4-triazole    (compound #226);-   5-amino-3-[1-methyl-1H-indazol-5-yl]amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #227);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(3-(2,2,2-trifluoroethoxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #228);-   5-amino-3-(benzofuran-5-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #229);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(4-(2,2,2-trifluoroethoxy)phenyl)carbonyl-1H-1,2,4-triazole    (compound #230);-   5-amino-1-(3-aminocarbonylmethoxy)phenylcarbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #231);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(4-iso-propylphenyl)carbonyl-1H-1,2,4-triazole    (compound #232);-   3-amino-5-(1,4-benzodioxan-6-yl)amino-1-(4-iso-propylphenyl)carbonyl-1H-1,2,4-triazole    (compound #233);-   5-amino-1-(3,4-dimethylphenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #234);-   5-amino-1-(3-methylphenyl)carbonyl-3-[3-(methylsulfonylmethoxy)phenyl]amino-1H-1,2,4-triazole    (compound #235);-   3-amino-1-(3,4-dimethylphenyl)carbonyl-5-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #236);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(4-thiomethylphenyl)carbonyl-1H-1,2,4-triazole    (compound #237);-   3-amino-5-(1,4-benzodioxan-6-yl)amino-1-(4-thiomethylphenyl)carbonyl-1H-1,2,4-triazole    (compound #238);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(3,5-dimethylphenyl)carbonyl-1H-1,2,4-triazole    (compound #239);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(4-nitrophenyl)carbonyl-1H-1,2,4-triazole    (compound #240);-   3-amino-5-(1,4-benzodioxan-6-yl)amino-1-[(4-fluoro-3-methyl)phenyl]carbonyl-1H-1,2,4-triazole    (compound #241);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-[(4-fluoro-3-methyl)phenyl]carbonyl-1H-1,2,4-triazole    (compound #242);-   5-amino-1-(4-aminophenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #243);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-[(4-trifluoromethyl)phenyl]carbonyl-1H-1,2,4-triazole    (compound #244);-   5-amino-1-(4-cyanophenyl)carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #245);-   1-[(4-Acetylamino)phenyl]carbonyl-5-amino-3-(1,4-benzodioxan-6-yl)-amino-1H-1,2,4-triazole    (compound #246);-   5-amino-1-[(4-dimethylamino)phenyl]carbonyl-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #247);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-[(4-methylsulfonyl)phenyl]carbonyl-1H-1,2,4-triazole    (compound #248);-   5-amino-1-[(3-chloro-4-methyl)phenyl]carbonyl-3-(1,4-benzodioxan-6-yl)-amino-1H-1,2,4-triazole    (compound #249);-   5-amino-3-(benzothiazol-6-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #250);-   5-amino-1-(3-methylphenyl)carbonyl-3-(6-quinolinyl)amino-1H-1,2,4-triazole    (compound #251);-   5-amino-3-(1H-indol-5-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #252);-   5-amino-3-(1H-2-methyl-indazol-6-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #253);-   5-amino-3-(1H-1-methyl-indazol-6-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #254);-   5-amino-3-(1H-2-methyl-indol-5-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #255);-   5-amino-3-(benzothiazol-2-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #256);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(3-methyl-4-methoxy)phenylcarbonyl-1H-1,2,4-triazole    (compound #257);-   5-amino-3-(1,4-benzodioxan-6-yl)amino-1-(3-methyl-4-iso-propoxy)phenylcarbonyl-1H-1,2,4-triazole    (compound #258);-   5-amino-3-(1,2-benzisothiazol-5-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #259);-   5-amino-3-(3-methyl-1,2-benzisothiazol-5-yl)amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #260);-   1-Acetyl-5-amino-3-(1,4-benzodioxan-6-yl)amino-1H-1,2,4-triazole    (compound #261);

5-amino-3-[4-[2-(pyrrolidin-1-yl)ethoxy]-3-fluorophenyl]amino-1-[4-(morpholin-4-yl)phenyl]carbonyl-1H-1,2,4-triazole(compound #262), ¹H-NMR (DMSO-d₆, 300 MHz) 9.21 (s, 1H), 8.20 (d, J=0.9Hz, 1H), 7.75 (m, 2H), 6.80-7.60 (m, 4H), 4.10 (m, 1H), 3.75 (m, 4H),3.30 (m, 5H), 3.20 (m, 2H), 2.95 (m, 2H), 2.85 (m, 1H), 2.40-2.60 (m,5H), 1.65 (m, 2H) ppm.

5-amino-1-(4-(tert-butyl)phenyl)carbonyl-3-[3-(1,3-oxazol-5-yl)phenylamino]-1H-1,2,4-triazole(compound #263), tan solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.48 (s, 1H), 8.39(s, 1H), 8.14 (d, J=8.4 Hz, 2H), 8.08 (s, 1H), 7.82 (s, 2H), 7.57 (d,J=8.4 Hz, 2H), 7.36 (s, 1H), 7.32-7.28 (m, 2H), 1.35 (s, 9H) ppm; MS(ES) 403.07 (M+H), 401.24 (M−H).

5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[3-(1,3-oxazol-5-yl)phenylamino]-1H-1,2,4-triazole(compound #264), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.33 (dt,J=9.0 Hz, 2.1 Hz, 2H), 8.03 (t, J=1.8 Hz, 1H), 7.89 (s, 1H), 7.32 (t,J=7.5 Hz, 2H), 7.25 (s, 1H), 7.11-7.08 (m, 3H), 6.72 (s, 2H), 1.48 (s,9H) ppm; MS (ES) 419.04 (M+H), 417.18 (M−H).

5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #265), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 11.59 (s,1H), 9.02 (s, 1H), 8.52 (s, 1H), 8.12 (s, 1H), 7.85-7.59 (m, 6H), 7.46(d, J=9.0 Hz, 2H), 6.83 (d, J=9.0 Hz, 2H), 6.55-6.54 (m, 1H), 3.99 (t,J=5.7 Hz, 2H), 3.56 (t, J=4.5 Hz, 4H), 2.64 (t, J=5.7 Hz, 2H), 2.45 (t,J=4.5 Hz, 4H) ppm; MS (ES) 448.108 (M+H), 446.23 (M−H).

5-amino-1-(4-(tert-butyl)phenyl)carbonyl-3-[4-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #266), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.02 (s, 1H),8.16-8.12 (m, 3H), 7.74 (s, 2H), 7.56 (d, J=8.7 Hz, 2H), 7.41 (d, J=8.7Hz, 2H), 6.82 (d, J=8.7 Hz, 2H), 4.00 (t, J=5.7 Hz, 2H), 3.56 (t, J=4.5Hz, 4H), 2.64 (t, J=5.7 Hz, 2H), 2.45 (t, J=4.5 Hz, 4H), 1.34 (s, 9H)ppm; MS (ES) 465.15 (M+H), 463.29 (M−H).

5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #267), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.02 (s,1H), 8.18 (d, J=8.7 Hz, 2H), 8.11 (s, 1H), 7.71 (s, 2H), 7.41 (d, J=8.7Hz, 2H), 7.32 (d, J=8.7 Hz, 2H), 6.82 (d, J=8.7 Hz, 2H), 4.00 (t, J=4.2Hz, 2H), 3.56 (t, J=3.6 Hz, 4H), 2.64 (t, J=5.7 Hz, 2H), 2.45 (t, J=4.5Hz, 4H), 1.42 (s, 9H) ppm; MS (ES) 481.18 (M+H), 479.25 (M−H).

5-amino-1-(4-(imidazol-1-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #268), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.09 (s, 1H),8.44 (s, 1H), 8.32 (d, J=9.0 Hz, 2H), 8.14 (s, 3H), 7.91 (s, 1H), 7.87(d, J=8.7 Hz, 2H), 7.78 (m, 2H), 7.42 (d, J=9.0 Hz, 2H), 7.15 (s, 1H),6.83 (d, J=9.3 Hz, 2H), 3.98 (t, J=6.7 Hz, 2H), 2.79 (t, J=6.7 Hz, 2H),2.55 (m, 4H), 1.68 (m, 4H) ppm; MS (ES) 459.08 (M+H), 457.22 (M−H).

5-amino-1-(4-(phenoxy)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #269), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.04 (s,1H), 8.25 (d, J=9.0 Hz, 2H), 8.17 (s, 1H), 7.74 (s, 1H), 7.49-7.39 (m,4H), 7.24 (t, J=7.2 Hz, 1H), 7.15 (d, J=8.7 Hz, 2H), 7.09 (d, J=7.2 Hz,2H), 6.81 (d, J=6.6 Hz, 2H), 3.99 (t, J=6.0 Hz, 2H), 2.81 (t, J=6.0 Hz,2H), 2.58 (m, 4H), 1.69 (m, 4H) ppm; MS (ES) 485.07 (M+H), 483.30 (M−H).

5-amino-1-(4-(tert-butoxycarbonylamino)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #270), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.78 (s, 1H),9.02 (s, 1H), 8.18-8.14 (m, 3H), 7.70 (s, 2H), 7.59 (d, J=9.0 Hz, 2H),7.41 (d, J=9.0 Hz, 2H), 6.81 (d, J=9.0 Hz, 2H), 4.00 (t, J=6.0 Hz, 2H),2.82 (t, J=6.0 Hz, 2H), 2.58 (m, 4H), 1.69 (m, 4H), 1.50 (s, 9H) ppm; MS(ES) 508.13 (M+H), 506.27 (M−H).

5-amino-1-(benzo[d]thiazol-6-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #271), off-white solid; pale yellow solid; ¹H-NMR (DMSO-d₆,300 MHz) 9.60 (s, 1H), 9.06 (d, J=9.0 Hz, 2H), 8.24 (q, J=8.4 Hz, 3H),8.14 (d, J=9.0 Hz, 1H), 7.80 (s, 2H), 7.41 (d, J=9.0 Hz, 2H), 6.78 (d,J=9.0 Hz, 2H), 3.97 (t, J=6.0 Hz, 2H), 2.78 (m, 2H), 1.68 (m, 4H) ppm;MS (ES) 450.04 (M+H), 448.22 (M−H).

5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenyl][methyl]amino-1H-1,2,4-triazole(compound #272), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.19 (d,J=8.7 Hz, 2H), 7.71 (s, 2H), 7.29 (d, J=8.7 Hz, 2H), 7.07 (d, J=8.7 Hz,2H), 6.88 (d, J=8.7 Hz, 2H), 4.04 (t, J=6.0 Hz, 2H), 3.29 (s, 3H), 2.78(t, J=6.0 Hz, 2H), 2.53 (m, 4H), 1.68 (m, 4H), 1.40 (s, 9H) ppm; MS (ES)479.13 (M+H).

5-amino-1-(4-(tert-butyl)phenyl)carbonyl-3-[4-((tert-butoxycarbonyl)aminochroman-6-yl]amino-1H-1,2,4-triazole(compound #273), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.97 (s,1H), 8.14 (d, J=8.4 Hz, 2H), 7.75 (m, 2H), 7.62 (d, J=8.4 Hz, 2H),7.33-7.27 (m, 3H), 6.62 (d, J=9.0 Hz, 1H), 6.78 (d, J=9.0 Hz, 2H), 4.64(m, 1H), 4.10 (t, J=5.3 Hz, 2H), 1.98 (m, 1H), 1.85 (m, 1H), 1.38 (s,9H), 1.34 (s, 9H) ppm; MS (ES) 507.70 (M+H), 505.73 (M−H).

5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-((tert-butoxycarbonyl)aminochroman-6-yl]amino-1H-1,2,4-triazole(compound #274), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.97 (s,1H), 8.28 (d, J=9.3 Hz, 2H), 7.72 (s, 2H), 7.38-7.25 (m, 3H), 7.08 (d,J=9.3 Hz, 2H), 6.64 (d, J=8.7 Hz, 1H), 4.81 (quint., J=6.0 Hz, 1H), 4.65(m, 1H), 4.10 (t, J=5.7 Hz, 2H), 1.98 (m, 1H), 1.85 (m, 1H), 1.32 (m,15H) ppm; MS (ES) 509.64 (M+H), 507.62 (M−H).

5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-((tert-butoxycarbonyl)aminochroman-6-yl]amino-1H-1,2,4-triazole(compound #275), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.97 (s,1H), 8.19 (d, J=9.0 Hz, 2H), 7.73 (s, 2H), 7.33-7.27 (m, 3H), 7.17 (d,J=8.7 Hz, 1H), 6.62 (d, J=9.0 Hz, 2H), 4.64 (m, 1H), 4.10 (t, J=4.8 Hz,2H), 1.98 (m, 1H), 1.84 (m, 1H), 1.40 (m, 18H) ppm; MS (ES) 523.70(M+H), 521.59 (M−H).

5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-((tert-butoxycarbonyl)aminochroman-6-yl]amino-1H-1,2,4-triazole(compound #276), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 11.53 (s,1H), 8.97 (s, 1H), 8.47 (s, 1H), 7.91 (d, J=7.5 Hz, 2H), 7.73 (s, 2H),7.66 (d, J=8.4 Hz, 1H) 7.61 (m, 1H), 7.49 (dd, J=8.7, 2.7 Hz, 1H), 7.32(d, J=8.7 Hz, 1H), 7.21 (s, 1H), 6.54 (d, J=8.7 Hz, 1H), 6.52 (s, 1H),4.64 (m, 1H), 4.10 (m, 2H), 1.98 (m, 1H), 1.85 (m, 1H), 1.39 (m, 9H)ppm; MS (ES) 490.61 (M+H), 488.55 (M−H).

5-amino-1-(4-(phenyl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #277), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.08 (s, 1H),8.28 (d, J=8.7 Hz, 2H), 8.16 (s, 1H), 7.86 (d, J=8.7 Hz, 2H), 7.80 (m,4H), 7.51 (t, J=7.2 Hz, 2H), 7.45-7.40 (m, 3H), 6.83 (d, J=9.3 Hz, 2H),3.99 (t, J=6.0 Hz, 2H), 2.80 (t, J=6.0 Hz, 2H), 2.56 (m, 4H), 1.68 (m,4H) ppm; MS (ES) 469.10 (M+H), 467.29 (M−H).

5-amino-1-[4-((tert-butoxycarbonyl)aminomethyl)phenyl]carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #278), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.05 (s, 1H),8.17 (s, 1H), 8.11 (d, J=8.1 Hz, 2H), 7.75 (s, 1H), 7.39 (t, J=6.0 Hz,4H), 6.79 (d, J=9.3 Hz, 2H), 4.21 (d, J=6.0 Hz, 2H), 4.00 (t, J=6.0 Hz,2H), 2.85 (t, J=6.0 Hz, 2H), 2.62 (m, 4H), 1.71 (m, 4H), 1.41 (s, 9H)ppm; MS (ES) 522.65 (M+H), 520.59 (M−H).

5-amino-1-(2,3-dihydrobenzofuran-5-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #279), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.04 (s, 1H),8.17 (m, 2H), 8.08 (dd, J=8.6, 2.0 Hz, 1H), 7.70 (s, 1H), 7.43 (d, J=9.3Hz, 2H), 6.94-6.82 (m, 3H), 4.67 (t, J=9.0 Hz, 2H), 4.00 (t, J=6.0 Hz,2H), 3.28 (t, J=8.7 Hz, 2H), 2.84 (t, J=6.0 Hz, 2H), 2.60 (m, 4H), 1.70(m, 4H) ppm; MS (ES) 435.58 (M+H), 433.46 (M−H).

5-amino-1-(4-(1,2,3-thiadiazol-4-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #280), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.81 (s,1H), 9.10 (s, 1H), 8.33 (s, 4H), 8.17 (s, 1H), 7.80 (s, 2H), 7.42 (d,J=9.0 Hz, 2H), 6.82 (d, J=9.0 Hz, 2H), 3.97 (t, J=6.0 Hz, 2H), 2.77 (t,J=6.0 Hz, 2H), 2.53 (m, 4H), 1.67 (m, 4H) ppm; MS (ES) 477.51 (M+H),475.47 (M−H).

5-amino-1-(1H-benzo[d][1,2,3]triazol-5-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #281), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.09 (s, 1H),8.93 (s, 1H), 8.16 (s, 1H), 8.11 (dd, J=8.7, 1.2 Hz, 1H), 7.97 (d, J=8.4Hz, 2H), 6.79 (d, J=9.0 Hz, 1H), 3.99 (t, J=5.7 Hz, 2H), 2.83 (t, J=5.7Hz, 2H), 2.60 (m, 4H), 1.70 (m, 4H) ppm; MS (ES) 434.56 (M+H), 432.51(M−H).

5-amino-1-(4-(pyrrol-1-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #282), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.09 (s,1H), 8.32 (d, J=9.0 Hz, 2H), 8.18 (s, 1H), 7.77 (m, 4H), 7.56 (m, 2H),7.43 (d, J=9.3 Hz, 2H), 6.85 (d, J=9.0 Hz, 2H), 4.01 (t, J=6.0 Hz, 2H),2.63 (m, 4H), 1.71 (m, 4H) ppm; MS (ES) 458.56 (M+H), 456.55 (M−H).

5-amino-1-(3-methylthien-2-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #283), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz), 9.80 (s,1H), 9.21 (s, 1H), 7.95 (d, J=5.4 Hz, 1H), 7.75 (s, 2H), 7.61 (d, J=9.0Hz, 2H), 7.13 (d, J=5.4 Hz, 1H), 6.97 (d, J=9.0 Hz, 2H), 4.24 (t, J=5.1Hz, 2H), 3.13 (m, 2H), 2.62 (s, 2H), 2.52 (s, 2H), 2.04-1.87 (m, 4H)ppm; MS (ES) 413.03 (M+H).

5-amino-1-(5-methylthien-2-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #284), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz), 9.63 (s,1H), 9.24 (s, 1H), 8.11 (d, J=3.9 Hz, 1H), 7.75 (s, 2H), 7.60 (d, J=9.0Hz, 2H), 7.03 (d, J=3.9 Hz, 1H), 6.99 (d, J=9.0 Hz, 2H), 4.25 (t, J=5.1Hz, 2H), 3.57 (m, 2H), 3.14 (m, 2H), 2.58 (s, 2H), 2.04-1.87 (m, 4H)ppm; MS (ES) 413.03 (M+H).

5-amino-1-(thien-2-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #285), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz), 8.50 (s,1H), 8.35 (dd, J=3.6, 1.2 Hz, 1H), 7.95 (dd, J=5.1, 1.2 Hz, 1H), 7.62(d, J=9.0 Hz, 2H), 7.25 (dd, J=5.1, 3.6 Hz, 1H), 7.01 (d, J=9.0 Hz, 2H),4.30 (t, J=5.4 Hz, 2H), 3.58 (t, J=5.4 Hz, 2H), 3.40 (m, 4H), 2.10 (m,4H) ppm; MS (ES) 399.03 (M+H), 397.04 (M−H).

5-amino-1-(4-(methylamino)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #286), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.48 (s,1H), 8.27-8.23 (m, 2H), 7.51 (d, J=9.0 Hz, 2H), 6.94 (d, J=9.0 Hz, 2H),6.61 (d, J=9.0 Hz, 2H), 4.27 (t, J=5.1 Hz, 2H), 3.56 (t, J=5.1 Hz, 2H),3.40 (s, 4H), 2.79 (s, 3H), 2.10 (m, 4H) ppm; MS (ES) 422.07 (M+H),420.24 (M−H).

5-amino-1-(4-(methylthio)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #287), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.05 (s,1H), 8.16 (m, 2H), 7.74 (s, 2H), 7.40 (m, 3H), 6.83 (d, J=9.0 Hz, 2H),3.99 (t, J=6.0 Hz, 2H), 2.79 (t, J=6.0 Hz, 2H), 2.57 (m, 7H), 1.69 (m,4H) ppm; MS (ES) 439.02 (M+H), 437.22 (M−H).

5-amino-1-(quinolin-6-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #288), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.11 (s, 1H),9.03 (dd, J=3.9, 1.2 Hz, 1H), 8.90 (d, J=1.5 Hz, 1H), 8.54 (d, J=9.0 Hz,1H), 8.38 (dd, J=9.0, 1.5 Hz, 1H), 8.17 (s, 1H), 8.13 (d, J=9.0 Hz, 1H),7.84 (s, 2H), 7.65 (dd, J=7.8, 3.9 Hz, 1H), 7.42 (d, J=9.0 Hz, 2H), 6.79(d, J=9.0 Hz, 2H), 4.00 (t, J=5.7 Hz, 2H), 2.86 (t, J=5.7 Hz, 2H), 2.63(m, 4H), 1.70 (m, 4H) ppm; MS (ES) 444.04 (M+H), 442.29 (M−H).

5-amino-1-(2,6-difluorophenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #289), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.09 (s,1H), 8.16 (s, 1H), 7.86 (s, 2H), 7.66 (m, 2H), 7.29 (d, J=8.4 Hz, 2H),7.22 (d, J=9.0 Hz, 1H), 6.70 (d, J=9.0 Hz, 2H), 3.96 (t, J=6.0 Hz, 2H),2.80 (t, J=6.0 Hz, 2H), 2.58 (m, 4H), 1.69 (m, 4H) ppm; MS (ES) 429.06(M+H), 427.18 (M−H).

5-amino-1-(4-(tert-butylcarbonylamino)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #290), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.52 (s,1H), 9.03 (s, 1H), 8.21 (d, J=9.0 Hz, 2H), 8.60 (s, 1H), 7.83 (d, J=8.4Hz, 2H), 7.72 (s, 2H), 7.42 (d, J=8.7 Hz, 2H), 6.81 (d, J=8.7 Hz, 2H),3.99 (t, J=5.7 Hz, 2H), 2.78 (t, J=6.0 Hz, 2H), 2.54 (m, 4H), 1.68 (m,4H), 1.25 (s, 9H) ppm; MS (ES) 492.13 (M+H), 490.30 (M−H).

5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #291), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.74 (s, 1H),8.18 (d, J=8.7 Hz, 2H), 7.67 (s, 2H), 7.33 (d, J=8.7 Hz, 2H), 7.11 (d,J=8.7 Hz, 2H), 6.44 (d, J=9.0 Hz, 2H), 3.14 (m, 4H), 1.91 (m, 4H), 1.41(s, 9H) ppm; MS (ES) 421.15 (M+H), 419.20 (M−H).

3-amino-1-(4-(tert-butoxy)phenyl)carbonyl-5-(4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #292), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.88 (s, 1H),8.15 (d, J=9.0 Hz, 2H), 7.50 (d, J=9.0 Hz, 2H), 7.07 (d, J=8.7 Hz, 2H),6.52 (d, J=9.0 Hz, 2H), 5.98 (s, 2H), 3.20 (m, 4H), 1.94 (m, 4H), 1.39(s, 9H) ppm; MS (ES) 421.13 (M+H).

5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #293), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.74 (s, 1H),8.24 (d, J=9.0 Hz, 2H), 7.66 (s, 2H), 7.34 (d, J=9.0 Hz, 2H), 7.04 (d,J=9.3 Hz, 2H), 6.46 (d, J=8.7 Hz, 2H), 4.78 (sept., J=6.0 Hz, 1H), 3.15(m, 4H), 1.91 (m, 4H), 1.31 (d, 6.0 Hz, 6H) ppm; MS (ES) 407.10 (M+H),405.06 (M−H).

3-amino-1-(4-(iso-propoxy)phenyl)carbonyl-5-(4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #294), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.91 (s, 1H),8.22 (d, J=8.7 Hz, 2H), 7.49 (d, J=8.7 Hz, 2H), 7.01 (d, J=8.7 Hz, 2H),6.51 (d, J=9.3 Hz, 2H), 5.97 (s, 2H), 4.75 (sept., 6.0 Hz, 1H), 3.20 (m,4H), 1.94 (m, 4H), 1.30 (d, 5.7 Hz, 6H) ppm; MS (ES) 407.10 (M+H).

5-amino-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-3-[4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #295), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.74 (s, 1H),7.98 (dd, J=8.7, 2.1 Hz, 1H), 7.67 (m, 3H), 7.33 (d, J=9.0 Hz, 2H), 7.07(d, J=8.4 Hz, 1H), 6.44 (d, J=9.0 Hz, 2H), 3.14 (m, 4H), 1.91 (m, 4H),1.45 (s, 6H) ppm; MS (ES) 448.06 (M+H), 446.15 (M−H).

3-amino-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-5-[4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #296), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 10.83 (s, 1H),9.84 (s, 1H), 7.91 (dd, J=8.4, 2.1 Hz, 1H), 7.68 (d, J=2.1 Hz, 1H), 7.49(d, J=9.0 Hz, 2H), 7.03 (d, J=8.7 Hz, 1H), 6.52 (d, J=9.0 Hz, 2H), 5.98(s, 2H), 3.20 (m, 4H), 1.94 (m, 4H), 1.44 (s, 6H) ppm; MS (ES) 448.12(M+H), 446.16 (M−H).

5-amino-1-(4-(tert-butyl)phenyl)carbonyl-3-[4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #297), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.74 (s, 1H),8.15 (d, J=8.7 Hz, 2H), 7.70 (s, 2H), 7.55 (d, J=8.7 Hz, 2H), 7.32 (d,J=8.7 Hz, 2H), 6.44 (d, J=9.0 Hz, 2H), 3.14 (m, 4H), 1.91 (m, 4H), 1.34(s, 9H) ppm; MS (ES) 404.13 (M+H).

3-amino-1-(4-(tert-butyl)phenyl)carbonyl-5-[4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #298), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.84 (s, 1H),8.03 (d, J=8.4 Hz, 2H), 7.51 (dd, J=8.7, 2.7 Hz, 4H), 6.52 (d, J=9.0 Hz,2H), 5.96 (s, 2H), 3.20 (m, 4H), 1.94 (m, 4H), 1.31 (s, 9H) ppm; MS (ES)404.15 (M+H).

5-amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #299), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.68 (s, 1H),8.26 (d, J=9.0 Hz, 2H), 7.59 (s, 2H), 7.37 (d, J=9.0 Hz, 2H), 6.76 (d,J=9.3 Hz, 2H), 6.47 (d, J=9.0 Hz, 2H), 3.16 (m, 4H), 3.04 (s, 6H), 1.92(m, 4H) ppm; MS (ES) 392.12 (M+H), 393.11 (M−H).

5-amino-1-(4-(methyl)phenyl)carbonyl-3-[4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #300), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.76 (s, 1H),8.04 (s, 1H), 7.92 (m, 1H), 7.69 (s, 2H), 7.43-7.41 (m, 2H), 7.33 (d,J=8.7 Hz, 2H), 6.42 (d, J=8.7 Hz, 2H), 3.13 (m, 4H), 2.41 (s, 3H), 1.91(m, 4H) ppm; MS (ES) 363.10 (M+H), 361.17 (M−H).

3-amino-1-(4-methylphenyl)carbonyl-5-(4-(pyrrolidin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #301), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.82 (s, 1H),7.88-7.84 (m, 2H), 7.50 (d, J=8.7 Hz, 2H), 7.40-7.37 (m, 2H), 6.50 (d,J=9.0 Hz, 2H), 5.98 (s, 2H), 3.20 (m, 4H), 2.37 (s, 3H), 1.94 (m, 4H)ppm; MS (ES) 363.10 (M+H), 361.29 (M−H).

5-amino-1-(4-(tert-butyl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #302), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (s, 1H),8.13 (d, J=8.4 Hz, 2H), 7.75 (s, 2H), 7.56 (d, J=8.4 Hz, 2H), 7.40 (d,J=8.7 Hz, 2H), 6.81 (d, J=9.0 Hz, 2H), 3.96 (t, J=5.7 Hz, 2H), 2.59 (t,J=5.7 Hz, 2H), 2.40 (m, 4H), 1.48 (m, 4H), 1.40-1.30 (m, 2H), 1.34 (s,9H) ppm; MS (ES) 463.15 (M+H), 461.22 (M−H).

3-amino-1-(4-(tert-butyl)phenyl)carbonyl-5-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #303), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.96 (s, 1H),8.02 (d, J=8.7 Hz, 2H), 7.64 (d, J=8.7 Hz, 2H), 7.52 (d, J=8.7 Hz, 2H),6.92 (d, J=9.0 Hz, 2H), 6.03 (s, 2H), 4.03 (t, J=6.0 Hz, 2H), 2.62 (t,J=6.0 Hz, 2H), 2.41 (m, 4H), 1.49 (m, 4H), 1.38 (m, 2H), 1.31 (s, 9H)ppm; MS (ES) 463.15 (M+H), 461.34 (M−H).

3-amino-1-(4-(morpholin-4-yl)phenyl)carbonyl-5-[3-fluoro-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #304), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 10.17 (s, 1H),8.22 (d, J=9.0 Hz, 2H), 7.86 (dd, J=13.8, 3.0 Hz, 1H), 7.40 (d, J=7.2Hz, 1H), 7.15 (t, J=9.1 Hz, 1H), 6.99 (d, J=9.3 Hz, 2H), 6.04 (s, 2H),4.14 (t, J=5.7 Hz, 2H), 3.73 (m, 4H), 3.33 (m, 4H), 2.91 (s, 2H), 2.64(s, 4H), 1.72 (m, 4H) ppm; MS (ES) 496.94 (M+H), 494.56 (M−H).

5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[3-fluoro-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #305), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.26 (s, 1H),8.12 (d, J=9.0 Hz, 2H), 7.74 (s, 2H), 7.49 (dd, J=13.8, 2.1 Hz, 1H),7.16-6.98 (m, 4H), 4.03 (t, J=6.0 Hz, 2H), 2.76 (t, J=5.7 Hz, 2H), 2.51(m, 4H), 1.67 (m, 4H), 1.41 (s, 9H) ppm; MS (ES) 483.14 (M+H), 481.30(M−H).

5-amino-1-(4-(1,2,3-thiadiazol-4-yl)phenyl)carbonyl-3-[3-fluoro-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #306), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.81 (d, J=1.2Hz, 1H), 9.31 (s, 1H), 8.30 (s, 4H), 8.14 (d, J=1.5 Hz, 1H), 7.83 (s,2H), 7.44 (dd, J=14.1, 1.8 Hz, 1H), 7.17 (d, J=10.2 Hz, 1H), 7.03 (t,J=9.1 Hz, 1H), 4.02 (t, J=6.0 Hz, 2H), 2.75 (t, J=6.0 Hz, 2H), 2.51 (m,4H), 1.65 (m, 4H) ppm; MS (ES) 495.05 (M+H), 493.14 (M−H).

5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[3-fluoro-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #307), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.25 (s, 1H),8.18 (d, J=8.7 Hz, 2H), 7.73 (s, 2H), 7.47 (dd, J=14.4, 2.4 Hz, 1H),7.17 (d, J=11.7 Hz, 1H), 7.08-7.02 (m, 3H), 4.76 (sept., J=6.1 Hz, 1H),4.04 (t, J=6.0 Hz, 2H), 2.77 (t, J=5.7 Hz, 2H), 2.53 (m, 4H), 1.67 (m,4H), 1.31 (d, J=5.7 Hz, 6H) ppm; MS (ES) 469.12 (M+H), 467.25 (M−H).

5-amino-1-(phenyl)carbonyl-3-[3-fluoro-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #308), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.27 (s, 1H),8.13-8.08 (m, 2H), 7.78 (s, 2H), 7.66-7.42 (m, 4H), 7.12-6.98 (m, 2H),4.03 (t, J=6.0 Hz, 2H), 2.76 (t, J=6.0 Hz, 2H), 2.51 (m, 4H), 1.67 (m,4H) ppm; MS (ES) 411.10 (M+H), 409.20 (M−H).

5-amino-1-(1H-indol-6-yl)carbonyl-3-[3-fluoro-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #309), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 11.55 (s, 1H),9.25 (s, 1H), 8.41 (s, 1H), 8.14 (s, 1H), 7.82 (dd, J=8.1, 1.2 Hz, 1H),7.74 (s, 2H), 7.65-7.60 (m, 2H), 7.47 (dd, J=14.1, 2.1 Hz, 1H), 7.20 (d,J=9.9 Hz, 1H), 7.04 (t, J=9.45 Hz, 1H), 6.54 (s, 1H), 4.03 (t, J=6.0 Hz,2H), 2.77 (t, J=6.0 Hz, 2H), 2.52 (m, 4H), 1.67 (m, 4H) ppm; MS (ES)450.09 (M+H), 448.24 (M−H).

5-amino-1-(3-(thiazol-2-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #310), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.12 (s, 1H),8.90 (s, 1H), 8.22-8.13 (m, 3H), 7.98 (d, J=3.0 Hz, 1H), 7.87-7.80 (m,3H), 7.68 (t, J=7.8 Hz, 1H), 7.44 (d, J=8.7 Hz, 2H), 6.69 (d, J=8.7 Hz,2H), 3.98 (t, J=5.7 Hz, 2H), 2.88 (t, J=5.7 Hz, 2H), 2.66 (m, 4H), 1.72(m, 4H) ppm; MS (ES) 476.01 (M+H), 474.17 (M−H).

5-amino-1-(4-(thien-2-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #311), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.07 (s, 1H),8.23 (d, J=8.4 Hz, 2H), 7.84 (d, J=8.4 Hz, 2H), 7.77 (s, 2H), 7.69 (m,1H), 7.42 (d, J=9.0 Hz, 2H), 7.19 (m, 1H), 6.83 (d, J=9.0 Hz, 2H), 3.99(t, J=6.0 Hz, 2H), 2.79 (t, J=6.0 Hz, 2H), 2.55 (m, 4H), 1.68 (m, 4H)ppm; MS (ES) 475.04 (M+H), 473.20 (M−H).

5-amino-1-(1,2,3-thiadiazol-4-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #312), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz), 8.15 (s,1H), 7.46 (d, J=8.7 Hz, 2H), 6.98 (d, J=8.7, 2H), 5.11 (s, 1H), 4.08 (t,J=5.7 Hz, 2H), 2.86 (t, J=5.7 Hz, 2H), 2.60 (m, 4H), 1.70 (m, 4H) ppm;MS (ES) 373.03 (M+H), 371.22 (M−H).

5-amino-1-(3-(thien-2-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #313), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.88 (s,1H), 8.32 (s, 1H), 7.76-7.70 (m, 2H), 7.59 (s, 2H), 7.40-7.22 (m, 2H),7.21 (d, J=9.0 Hz, 2H), 6.96-6.94 (m, 1H), 6.46 (d, J=9.0 Hz, 2H), 3.74(t, J=5.7 Hz, 2H), 2.64 (t, J=5.7 Hz, 2H), 2.41 (m, 4H), 1.49 (m, 4H)ppm; MS (ES) 475.04 (M+H), 473.14 (M−H).

5-amino-1-(4-(thien-3-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #314), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.07 (s,1H), 8.23 (d, J=8.4 Hz, 2H), 8.10 (t, J=2.1 Hz, 1H), 7.91 (d, J=8.7 Hz,2H), 7.77 (s, 2H), 7.69 (m, 1H), 7.42 (d, J=8.7 Hz, 2H), 6.83 (d, J=8.7Hz, 2H), 3.99 (t, J=6.0 Hz, 2H), 2.80 (t, J=6.0 Hz, 2H), 2.56 (m, 4H),1.68 (m, 4H) ppm; MS (ES) 475.04 (M+H), 473.24 (M−H).

5-amino-1-(4-(tert-butyl)phenyl)carbonyl-3-[3-methoxy-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #315), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.10 (s,1H), 8.08 (d, J=8.1 Hz, 2H), 7.77 (s, 2H), 7.51 (d, J=8.1 Hz, 2H), 7.50(s, 1H), 6.85-6.77 (m, 2H), 3.98 (t, J=6.0 Hz, 2H), 3.62 (s, 3H), 2.89(t, J=6.0 Hz, 2H), 2.69 (m, 4H), 1.73 (m, 4H), 1.31 (s, 9H) ppm; MS (ES)479.13 (M+H), 477.30 (M−H).

5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[3-methoxy-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #316), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.06 (s,1H), 8.22 (d, J=8.4 Hz, 2H), 7.71 (s, 2H), 7.42 (d, J=1.8 Hz, 1H), 7.01(d, J=8.7 Hz, 2H), 6.85-6.77 (m, 2H), 4.75 (sept., J=2.7 Hz, 1H), 3.97(t, J=6.0 Hz, 2H), 3.68 (s, 3H), 2.82 (t, J=6.0 Hz, 2H), 2.60 (m, 4H),1.70 (m, 4H), 1.31 (d, J=2.7 Hz, 6H) ppm; MS (ES) 481.08 (M+H).

5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[3-methoxy-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #317), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.10 (s,1H), 8.22 (s, 1H), 8.18 (d, J=8.7 Hz, 2H), 7.77 (s, 2H), 7.51 (d, J=8.1Hz, 2H), 7.45 (s, 1H), 7.08 (d, J=8.7 Hz, 2H), 6.84 (s, 2H), 3.99 (t,J=6.0 Hz, 2H), 3.67 (s, 3H), 2.91 (t, J=6.0 Hz, 2H), 2.69 (m, 4H), 1.73(m, 4H), 1.31 (s, 9H) ppm; MS (ES) 495.11 (M+H), 493.29 (M−H).

5-amino-1-(1H-indol-6-yl)carbonyl-3-[3-methoxy-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #318), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 11.54 (s,1H), 9.06 (s, 1H), 8.42 (s, 1H), 8.20 (s, 1H), 7.84 (d, J=7.5 Hz, 1H),7.72-7.59 (m, 4H), 7.43 (d, J=2.1 Hz, 1H), 6.91 (dd, J=7.5, 2.1 Hz, 1H),6.84 (d, J=9.0 Hz, 1H), 6.53 (s, 1H), 3.97 (t, J=6.0 Hz, 2H), 3.51 (s,3H), 2.86 (t, J=6.0 Hz, 2H), 2.65 (m, 4H), 1.71 (m, 4H) ppm; MS (ES)462.08 (M+H), 460.22 (M−H).

-   5-amino-1-(4-(1,2,3-thiadiazol-4-yl)phenyl)carbonyl-3-[3-methoxy-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole    (compound #319);

5-amino-1-(4-(tert-butyl)phenyl)carbonyl-3-[4-[2-(azepan-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #320), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (s,1H), 8.17 (s, 1H), 8.14 (d, J=8.4 Hz, 2H), 7.75 (s, 2H), 7.56 (d, J=8.4Hz, 1H), 7.41 (d, J=9.0 Hz, 2H), 6.81 (d, J=8.7 Hz, 2H), 3.98 (t, J=6.0Hz, 2H), 2.88 (t, J=6.0 Hz, 2H), 2.74 (m, 4H), 1.59-1.54 (m, 8H), 1.33(s, 9H) ppm; MS (ES) 477.18 (M+H), 475.33 (M−H).

5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-[2-(azepan-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #321), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (s,1H), 8.24 (d, J=9.0 Hz, 2H), 8.17 (s, 1H), 7.71 (s, 2H), 7.42 (d, J=9.0Hz, 2H), 7.05 (d, J=9.0 Hz, 2H), 6.83 (d, J=9.0 Hz, 2H), 4.77 (sept.,J=6.0 Hz, 1H), 3.98 (t, J=6.0 Hz, 2H), 2.87 (t, J=6.0 Hz, 2H), 2.73 (t,J=5.1 Hz, 4H), 1.59-1.54 (m, 8H), 1.31 (d, J=6.0 Hz, 6H) ppm; MS (ES)479.13 (M+H), 477.28 (M−H).

5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-[2-(azepan-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #322), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (s,1H), 8.17 (s, 1H), 8.16 (d, J=8.4 Hz, 2H), 7.72 (s, 2H), 7.42 (d, J=8.7Hz, 1H), 7.12 (d, J=8.1 Hz, 2H), 6.82 (d, J=8.7 Hz, 2H), 3.98 (t, J=6.0Hz, 2H), 2.88 (t, J=6.0 Hz, 2H), 2.74 (t, J=5.3 Hz, 4H), 1.59-1.54 (m,8H), 1.42 (s, 9H) ppm; MS (ES) 493.16 (M+H), 491.33 (M−H).

5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-(azepan-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #323), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 11.60 (s,1H), 9.02 (s, 1H), 8.51 (s, 1H), 8.14 (s, 1H), 7.84 (dd, J=8.1, 1.5 Hz,1H), 7.72 (s, 2H), 7.63-7.60 (m, 2H), 7.46 (d, J=9.0 Hz, 2H), 6.83 (d,J=9.0 Hz, 2H), 6.54 (s, 1H), 3.96 (t, J=6.0 Hz, 2H), 2.84 (t, J=6.0 Hz,2H), 2.70 (t, J=5.3 Hz, 4H), 1.59-1.54 (m, 8H) ppm; MS (ES) 460.10(M+H), 458.34 (M−H).

5-amino-1-(4-(1,2,3-thiadiazol-4-yl)phenyl)carbonyl-3-[4-[2-(azepan-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #324), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.81 (s,1H), 9.09 (s, 1H), 8.33 (s, 4H), 7.80 (s, 2H), 7.42 (d, J=8.7 Hz, 2H),6.82 (d, J=8.7 Hz, 2H), 3.96 (t, J=6.0 Hz, 2H), 2.85 (t, J=6.0 Hz, 2H),2.71 (t, J=5.1 Hz, 4H), 1.59-1.54 (m, 8H) ppm; MS (ES) 505.05 (M+H),503.23 (M−H).

5-amino-N-(2,4,6-trifluorophenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carbothioamide(compound #325), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.14 (s,1H), 8.35 (s, 2H), 8.14 (s, 1H), 7.60 (d, J=9.0 Hz, 2H) 7.39-7.32 (m,2H), 6.81 (d, J=9.0 Hz, 2H), 4.01 (t, J=6.0 Hz, 2H), 2.84 (t, J=6.0 Hz,2H), 2.60 (m, 4H), 1.71 (m, 4H) ppm; MS (ES) 478.02 (M+H), 476.25 (M−H).

5-amino-N-(2,6-difluorophenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carbothioamide(compound #326), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.13 (s,1H), 8.35 (s, 2H), 8.16 (s, 1H), 7.60 (d, J=9.0 Hz, 2H) 7.47-7.36 (m,2H), 7.22 (t, J=8.0 Hz, 2H), 6.80 (d, J=9.0 Hz, 2H), 4.00 (t, J=6.0 Hz,2H), 2.81 (t, J=6.0 Hz, 2H), 2.57 (m, 4H), 1.69 (m, 4H) ppm; MS (ES)460.03 (M+H).

5-amino-1-(4-(morpholin-4-yl)phenyl)carbonyl-3-[4-[2-(isoindolin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #327), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.00 (s, 1H),8.25 (d, J=9.3 Hz, 2H), 8.14 (s, 1H), 7.66 (s, 2H), 7.47 (d, J=9.0 Hz,2H), 7.23-7.14 (m, 4H), 7.03 (d, J=9.0 Hz, 2H), 6.88 (d, J=9.3 Hz, 2H),4.07 (t, J=5.7 Hz, 2H), 3.93 (s, 4H), 3.74 (t, J=4.8 Hz, 4H), 3.33 (t,J=4.8 Hz, 4H), 3.04 (t, J=5.7 Hz, 2H) ppm; MS (ES) 526.10 (M+H).

5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-[2-(isoindolin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #328), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (s,1H), 8.24 (d, J=9.0 Hz, 2H), 8.14 (s, 1H), 7.70 (s, 2H), 7.44 (d, J=9.0Hz, 2H), 7.22-7.17 (m, 4H), 7.06 (d, J=9.0 Hz, 2H), 6.88 (d, J=9.0 Hz,2H), 4.77 (sept., J=6.0 Hz, 1H), 4.07 (t, J=5.7 Hz, 2H), 3.94 (s, 4H),3.04 (t, J=5.7 Hz, 2H), 1.31 (d, J=6.0 Hz, 6H) ppm; MS (ES) 499.08(M+H), 497.37 (M−H).

5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-[2-(isoindolin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #329), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (s,1H), 8.18 (d, J=8.7 Hz, 2H), 8.13 (s, 1H), 7.72 (s, 2H), 7.43 (d, J=9.0Hz, 2H), 7.20-7.11 (m, 6H), 6.85 (d, J=9.0 Hz, 2H), 4.07 (t, J=5.7 Hz,2H), 3.94 (s, 4H), 3.04 (t, J=5.7 Hz, 2H), 1.41 (s, 9H) ppm; MS (ES)513.11 (M+H), 511.27 (M−H).

5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-(isoindolin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #330), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 11.61 (s,1H), 9.02 (s, 1H), 8.52 (s, 1H), 8.18 (s, 2H), 7.84 (dd, J=8.3, 1.4 Hz,1H), 7.72 (s, 2H), 7.66-7.42 (m, 4H), 7.22-7.14 (m, 2H), 6.87 (d, J=8.7Hz, 2H), 6.54 (s, 1H), 4.07 (t, J=5.7 Hz, 2H), 3.93 (s, 4H), 3.03 (t,J=5.7 Hz, 2H), 2.97 (s, 4H) ppm; MS (ES) 480.04 (M+H), 478.25 (M−H).

5-amino-1-(3-(morpholin-4-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #331), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.06 (s,1H), 8.19 (s, 2H), 7.77 (d, J=12.0, 2H), 7.65-7.21 (m, 4H), 6.77 (d,J=9.0 Hz, 2H), 3.97 (t, J=5.7 Hz, 2H), 3.73 (m, 4H), 3.16 (m, 4H), 2.76(t, J=5.7 Hz, 2H), 2.53 (m, 4H), 1.67 (m, 4H) ppm; MS (ES) 478.08 (M+H),476.31 (M−H).

5-amino-1-[4-(2-(morpholin-4-yl)ethoxy)phenyl]carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #332), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.06 (s,1H), 8.25 (d, J=9.0 Hz, 2H), 7.72 (s, 2H), 7.44 (d, J=9.0 Hz, 2H), 7.09(d, J=9.0 Hz, 2H), 6.85 (d, J=9.0 Hz, 2H), 4.20 (t, J=5.6 Hz, 2H), 4.06(t, J=5.7 Hz, 2H), 3.57 (m, 4H), 3.00 (t, J=5.6 Hz, 2H), 2.78-2.69 (m,6H), 1.76 (m, 4H) ppm; MS (ES) 522.08 (M+H), 520.22 (M−H).

5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-(phenylamino)-1H-1,2,4-triazole(compound #333), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.25 (s,1H), 8.23 (d, J=8.7 Hz, 2H), 7.74 (s, 2H), 7.52 (d, J=8.4 Hz, 2H), 7.22(t, J=5.1 Hz, 2H), 7.06 (d, J=8.7 Hz, 2H), 6.83 (t, J=7.5 Hz, 1H), 4.79(sept., J=6.0 Hz, 1H), 1.32 (d, J=6.0 Hz, 6H) ppm; MS (ES) 338.05 (M+H).

5-amino-1-(4-(1,2,3-thiadiazol-4-yl)phenyl)carbonyl-3-(phenylamino)-1H-1,2,4-triazole(compound #334), off-white solid; off-white solid; ¹H-NMR (DMSO-d₆, 300MHz) 9.83 (s, 1H), 9.31 (s, 1H), 8.33 (s, 4H), 7.84 (s, 2H) 7.51 (d,J=8.1 Hz, 2H), 7.20 (t, J=7.7 Hz, 2H), 6.82 (t, J=7.7 Hz, 1H) ppm; MS(ES) 364.02 (M+H), 362.07 (M−H).

5-amino-1-(4-(morpholin-4-yl)phenyl)carbonyl-3-(phenylamino)-1H-1,2,4-triazole(compound #335), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.23 (s,1H), 8.24 (d, J=9.3 Hz, 2H), 7.71 (s, 2H), 7.53 (d, J=7.8 Hz, 2H), 7.23(t, J=8.0 Hz, 2H), 7.04 (d, J=9.0 Hz, 2H), 6.83 (t, J=7.4 Hz, 1H), 3.75(t, J=4.8 Hz, 4H), 3.34 (t, J=4.8 Hz, 4H) ppm; MS (ES) 365.08 (M+H).

5-amino-1-(3-(morpholin-4-yl)phenyl)carbonyl-3-(phenylamino)-1H-1,2,4-triazole(compound #336), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.28 (s,1H), 7.79 (s, 2H), 7.58-7.25 (m, 6H), 7.17 (t, J=8.0 Hz, 2H), 6.83 (t,J=7.2 Hz, 1H), 3.74 (m, 4H), 3.18 (m, 4H) ppm; MS (ES) 365.07 (M+H),363.26 (M−H).

5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-[2-(pyrrolidin-2-on-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #337), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.05 (s,1H), 8.24 (d, J=9.0 Hz, 2H), 7.72 (s, 2H), 7.43 (d, J=9.0 Hz, 2H), 7.08(d, J=9.0 Hz, 2H), 6.84 (d, J=9.0 Hz, 2H), 4.79 (sept., J=6.0 Hz, 1H),4.00 (t, J=5.6 Hz, 2H), 3.50 (t, J=5.7 Hz, 2H), 3.41 (t, J=6.9 Hz, 2H),2.21 (t, J=8.1 Hz, 2H), 1.91 (t, J=7.7 Hz, 2H), 1.32 (d, J=6.0 Hz, 6H)ppm; MS (ES) 465.07 (M+H).

5-amino-1-(4-(1,2,3-thiadiazol-4-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-2-on-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #338), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.82 (s,1H), 9.12 (s, 1H), 8.33 (s, 4H), 7.82 (s, 2H), 7.43 (d, J=9.0 Hz, 2H),6.83 (d, J=9.0 Hz, 2H), 3.98 (t, J=5.4 Hz, 2H), 3.48 (t, J=5.6 Hz, 2H),3.41 (t, J=6.9 Hz, 2H), 2.20 (t, J=8.1 Hz, 2H), 1.89 (quint., J=7.5 Hz,2H) ppm; MS (ES) 491.01 (M+H), 489.18 (M−H).

5-amino-1-(4-(morpholin-4-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-2-on-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #339), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (s,1H), 8.25 (d, J=8.4 Hz, 2H), 7.68 (s, 2H), 7.46 (d, J=8.7 Hz, 2H), 7.04(d, J=8.7 Hz, 2H), 6.86 (d, J=8.4 Hz, 2H), 4.00 (t, J=5.4 Hz, 2H), 3.75(m, 4H), 3.51 (t, J=5.6 Hz, 2H), 3.44 (t, J=6.9 Hz, 2H), 3.32 (m, 4H),2.22 (m, 2H), 1.91 (m, 2H) ppm; MS (ES) 492.07 (M+H), 490.13 (M−H).

5-amino-1-(3-(morpholin-4-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-2-on-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #340), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.08 (s,1H), 7.77 (s, 2H), 7.51 (d, J=8.4 Hz, 1H), 7.44-7.39 (m, 3H), 7.23 (d,J=8.4 Hz, 1H), 6.78 (d, J=9.0 Hz, 2H), 3.99 (t, J=5.1 Hz, 2H), 3.74 (m,4H), 3.50 (t, J=5.1 Hz, 2H), 3.43 (t, J=6.9 Hz, 2H), 3.17 (m, 4H), 2.21(t, J=8.1 Hz, 2H), 1.90 (quint., J=7.5 Hz, 2H) ppm; MS (ES) 492.06(M+H).

5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-(phenylamino)-1H-1,2,4-triazole(compound #341), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 10.17 (s,1H), 9.25 (s, 1H), 8.16 (d, J=8.0 Hz, 2H), 7.75 (s, 2H), 7.51 (d, J=7.5Hz, 2H), 7.20 (t, J=8.0 Hz, 2H), 7.13 (d, J=9.0 Hz, 2H), 6.82 (t, J=7.4Hz, 1H), 1.41 (s, 9H) ppm; MS (ES) 352.08 (M+H), 350.16 (M−H).

5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-[2-(pyrrolidin-2-on-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #342), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.06 (s,1H), 8.18 (d, J=8.4 Hz, 2H), 7.73 (s, 2H), 7.42 (d, J=8.7 Hz, 2H), 7.12(d, J=9.0 Hz, 2H), 6.83 (d, J=8.7 Hz, 2H), 3.99 (t, J=5.6 Hz, 2H), 3.50(t, J=5.4 Hz, 2H), 3.43 (t, J=6.9 Hz, 2H), 2.21 (t, J=8.0 Hz, 2H), 1.91(t, J=7.5 Hz, 2H), 1.42 (s, 9H) ppm; MS (ES) 479.07 (M+H), 477.25 (M−H).

5-amino-1-(4-(morpholin-4-yl)phenyl)carbonyl-3-[3-methoxy-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #343), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.06 (s,1H), 8.26-8.21 (m, 2H), 7.69 (s, 2H), 7.46-7.36 (m, 1H), 6.99 (d, J=8.7Hz, 2H), 6.87-6.84 (m, 1H), 3.99 (m, 2H), 3.75 (m, 4H), 3.70 (s, 3H),3.31 (t, J=4.7 Hz, 4H), 2.89 (t, J=6.0 Hz, 2H), 2.68 (m, 4H), 1.73 (m,4H) ppm; MS (ES) 441.07 (M+H), 439.25 (M−H).

5-amino-1-(3-(morpholin-4-yl)phenyl)carbonyl-3-[3-methoxy-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #344), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.10 (s,1H), 8.22 (s, 1H), 7.76 (s, 2H), 7.62 (s, 1H), 7.55 (d, J=7.5 Hz, 1H),7.43-7.14 (m, 1H), 6.98-6.91 (m, 2H), 6.81 (d, J=8.7 Hz, 2H), 4.00 (t,J=6.8 Hz, 2H), 3.73 (m, 4H), 3.60 (s, 3H), 3.14 (m, 4H), 2.96 (m, 2H),2.76 (m, 4H), 1.75 (m, 4H) ppm; MS (ES) 441.07 (M+H), 439.26 (M−H).

3-amino-1-(4-(tert-butoxy)phenyl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2-yl)amino]-1H-1,2,4-triazole(compound #345), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.69 (d,J=8.4 Hz, 1H), 8.08 (d, J=8.7 Hz, 2H), 7.59 (br. s, 1H), 7.08 (br. s,1H), 7.04 (d, J=8.7 Hz, 2H), 6.30-6.28 (m, 1H), 6.23-6.20 (m, 1H), 5.86(br. s, 2H), 3.91 (t, J=8.1 Hz, 1H), 2.80 (d, J=8.1 Hz, 2H), 2.46-2.40(m, 1H), 2.15 (d, J=8.1 Hz, 1H), 1.45-1.40 (m, 1H), 1.38 (s, 9H) ppm; MS(ES) 411.14 (M+H), 409.16 (M−H).

5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[(5-(aminocarbonyl)bicyclo[2.2.1]hept-2-en-6-yl)amino]-1H-1,2,4-triazole(compound #346), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.16 (d,J=8.7 Hz, 2H), 7.65 (br. s, 2H), 7.54 (br. s, 1H), 7.07 (d, J=8.4 Hz,2H), 7.04 (br. s, 1H), 6.25-6.21 (m, 1H), 6.20-6.14 (m, 1H), 5.83 (d,J=8.7 Hz, 2H), 3.64 (t, J=8.1 Hz, 1H), 2.80 (d, J=12.9 Hz, 2H),2.44-2.40 (m, 1H), 2.11 (d, J=9.0 Hz, 1H), 1.39 (s, 9H), 1.36-1.32 (m,1H) ppm; MS (ES) 411.23 (M+H), 409.16 (M−H).

3-amino-1-(3-(tert-butoxy)phenyl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2-yl)amino]-1H-1,2,4-triazole(compound #347), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.71 (d,J=8.4 Hz, 1H), 7.73 (d, J=7.2 Hz, 1H), 7.60 (br. s, 2H), 7.36 (t, J=7.8Hz, 1H), 7.16 (d, J=8.4 Hz, 2H), 7.10 (br. s, 1H), 6.30-6.28 (m, 1H),6.23-6.20 (m, 1H), 5.88 (br. s, 2H), 3.90 (t, J=8.1 Hz, 1H), 2.82 (br.s, 2H), 2.46-2.40 (m, 1H), 2.16 (d, J=7.8 Hz, 1H), 1.42 (d, J=8.7 Hz,1H), 1.30 (s, 9H) ppm; MS (ES) 411.20 (M+H), 409.14 (M−H).

5-amino-1-(3-(tert-butoxy)phenyl)carbonyl-3-[(5-(aminocarbonyl)bicyclo[2.2.1]hept-2-en-6-yl)amino]-1H-1,2,4-triazole(compound #348), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 7.84 (s,1H), 7.76 (d, J=7.2 Hz, 1H), 7.68 (br. s, 2H), 7.51 (br. s, 1H), 7.41(t, J=7.8 Hz, 2H), 7.19 (d, J=7.8 Hz, 1H), 7.04 (br. s, 1H), 6.25-6.20(m, 1H), 6.16-6.12 (m, 1H), 5.88 (d, J=9.0 Hz, 2H), 3.63 (t, J=8.1 Hz,1H), 2.77 (d, J=17.7 Hz, 2H), 2.41 (d, J=8.1 Hz, 1H), 2.09 (d, J=8.4 Hz,1H), 1.40-1.35 (m, 1H), 1.32 (s, 9H) ppm; MS (ES) 411.18 (M+H), 409.16(M−H).

3-amino-1-(4-(dimethylamino)phenyl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2-yl)amino]-1H-1,2,4-triazole(compound #349), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.65 (d,J=8.4 Hz, 1H), 8.17 (d, J=9.0 Hz, 2H), 7.55 (br. s, 1H), 7.05 (br. s,1H), 6.68 (d, J=9.3 Hz, 2H), 6.29 (dd, J=5.4, 2.1 Hz, 1H), 6.21 (dd,J=5.4, 2.1 Hz, 1H), 5.77 (br. s, 2H), 3.92 (t, J=8.4 Hz, 1H), 3.00 (s,6H), 2.78 (d, J=12.6 Hz, 2H), 2.49-2.47 (m, 1H), 2.15 (d, J=9.0 Hz, 1H),1.41 (d, J=9.0 Hz, 1H) ppm; MS (ES) 382.15 (M+H), 380.13 (M−H).

5-amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[(5-(aminocarbonyl)bicyclo[2.2.1]hept-2-en-6-yl)amino]-1H-1,2,4-triazole(compound #350), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.22 (d,J=8.7 Hz, 2H), 7.55 (br. s, 2H), 7.54 (br. s, 1H), 7.03 (br. s, 1H),6.72 (d, J=9.0 Hz, 2H), 6.22 (br. s, 2H), 5.74 (d, J=9.3 Hz, 1H), 3.66(t, J=9.0 Hz, 1H), 3.01 (s, 6H), 2.75 (d, J=9.6 Hz, 2H), 2.44 (d, J=8.4Hz, 1H), 2.11 (d, J=8.4 Hz, 1H), 1.35 (d, J=8.4 Hz, 9H) ppm; MS (ES)382.16 (M+H), 380.23 (M−H).

3-amino-1-(3-(dimethylamino)phenyl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2-yl)amino]-1H-1,2,4-triazole(compound #351), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.69 (d, J=8.4Hz, 1H), 7.60 (br. s, 1H), 7.33 (d, J=8.1 Hz, 1H), 7.26 (s, 1H), 7.22(d, J=8.7 Hz, 1H), 7.09 (br. s, 1H), 6.89 (dm, J=7.2 Hz, 1H), 7.10 (br.s, 1H), 6.31 (dd, J=8.4, 3.3 Hz, 1H), 6.22 (dd, J=8.4, 3.0 Hz, 1H), 5.83(br. s, 2H), 3.90 (t, J=7.5 Hz, 1H), 2.91 (s, 6H), 2.80 (d, J=6.3 Hz,2H), 2.49-2.47 (m, 1H), 2.16 (d, J=8.7 Hz, 1H), 1.42 (d, J=6.3 Hz, 1H)ppm; MS (ES) 382.16 (M+H), 380.25 (M−H).

5-amino-1-(3-(dimethylamino)phenyl)carbonyl-3-[(5-(aminocarbonyl)bicyclo[2.2.1]hept-2-en-6-yl)amino]-1H-1,2,4-triazole(compound #352), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 7.65 (br.s, 2H), 7.59 (s, 1H), 7.52 (br. s, 1H), 7.35 (d, J=8.1 Hz, 1H), 7.28 (t,J=7.8 Hz, 1H), 7.04 (br. s, 1H), 6.94 (d, J=8.4 Hz, 1H), 6.23 (dd,J=5.4, 2.7 Hz, 1H), 6.11 (dd, J=5.4, 3.0 Hz, 1H), 5.86 (d, J=9.0 Hz,1H), 3.61 (t, J=9.6 Hz, 1H), 2.93 (s, 6H), 2.74 (d, J=8.4 Hz, 2H), 2.41(d, J=7.2 Hz, 1H), 2.08 (d, J=8.4 Hz, 1H), 1.35 (d, J=9.0 Hz, 1H) ppm;MS (ES) 382.23 (M+H), 380.55 (M−H).

3-amino-1-(4-(iso-propoxy)phenyl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2-yl)amino]-1H-1,2,4-triazole(compound #353), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.68 (d,J=8.7 Hz, 1H), 8.15 (d, J=8.7 Hz, 2H), 7.58 (br. s, 1H), 7.07 (br. s,1H), 6.96 (d, J=8.7 Hz, 2H), 6.30-6.24 (m, 1H), 6.24-6.17 (m, 1H), 5.85(br. s, 2H), 4.72 (quint. J=5.4 Hz, 1H), 3.92 (t, J=7.2 Hz, 1H), 2.79(d, J=8.7 Hz, 2H), 2.50-2.46 (m, 1H), 2.15 (d, J=8.7 Hz, 1H), 1.41 (d,J=7.2 Hz, 1H), 1.28 (d, J=5.4 Hz, 6H) ppm; MS (ES) 397.15 (M+H), 395.15(M−H).

5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[(5-(aminocarbonyl)bicyclo[2.2.1]hept-2-en-6-yl)-amino]-1H-1,2,4-triazole(compound #354), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.21 (d,J=8.7 Hz, 1H), 7.63 (br. s, 2H), 7.53 (br. s, 1H), 7.03 (br. s, 1H),7.01 (d, J=9.0 Hz, 2H), 6.24-6.16 (m, 2H), 5.82 (d, J=9.0 Hz, 2H), 4.74(quint. J=6.0 Hz, 1H), 3.64 (t, J=8.1 Hz, 1H), 2.74 (d, J=9.3 Hz, 2H),2.43 (d, J=8.7 Hz, 1H), 2.10 (d, J=7.5 Hz, 1H), 1.35 (d, J=9.4 Hz, 1H),1.29 (d, J=5.7 Hz, 6H) ppm; MS (ES) 397.23 (M+H), 395.08 (M−H).

3-amino-1-(1H-indol-6-yl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2-yl)amino]-1H-1,2,4-triazole(compound #355), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 11.49 (s,1H), 8.72 (d, J=8.7 Hz, 1H), 8.37 (s, 1H), 7.74 (d, J=8.1 Hz, 1H), 7.57(d, J=7.8 Hz, 2H), 7.56 (s, 1H), 7.09 (br. s, 1H), 6.49 (br. s, 1H),6.32-6.27 (m, 1H), 6.26-6.20 (m, 1H), 5.82 (br. s, 2H), 3.94 (t, J=9.0Hz, 1H), 2.82 (br. s, 2H), 2.52 (br. s, 1H), 2.18 (d, J=8.7 Hz, 1H),1.43 (d, J=8.1 Hz, 1H) ppm; MS (ES) 377.98 (M+H), 376.09 (M−H).

5-amino-1-(1H-indol-6-yl)carbonyl-3-[(5-(aminocarbonyl)bicyclo[2.2.1]hept-2-en-6-yl)amino]-1H-1,2,4-triazole(compound #356), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 11.54 (s,1H), 8.52 (s, 1H), 7.77 (d, J=8.4 Hz, 1H), 7.66 (br. s, 2H), 7.62-7.55(m, 3H), 7.05 (br. s, 1H), 6.51 (br. s, 1H), 6.21 (s, 2H), 5.80 (d,J=9.3 Hz, 1H), 3.67 (t, J=9.3 Hz, 1H), 2.76 (br. s, 2H), 2.44 (d, J=8.7Hz, 1H), 2.12 (d, J=8.7 Hz, 1H), 1.36 (d, J=8.7 Hz, 1H) ppm; MS (ES)378.16 (M+H), 376.15 (M−H).

5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #357), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.95 (s,1H), 8.18 (d, J=9.0 Hz, 2H), 7.71 (br. s, 2H), 7.37 (d, J=8.4 Hz, 2H),7.12 (d, J=9.0 Hz, 2H), 6.82 (d, J=8.7 Hz, 2H), 3.05-2.95 (m, 4H),2.45-2.40 (m, 4H), 2.21 (s, 3H), 1.42 (s, 9H) ppm; MS (ES) 450.27 (M+H),448.07 (M−H).

5-amino-1-(3-(tert-butoxy)phenyl)carbonyl-3-[4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #358), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.99 (s,1H), 7.84 (d, J=7.5 Hz, 1H), 7.79 (s, H), 7.75 (br. s, 2H), 7.45 (t,J=8.1 Hz, 1H), 7.36 (d, J=9.0 Hz, 2H), 7.25 (dm, J=8.1 Hz, 1H), 6.79 (d,J=9.0 Hz, 2H), 3.02 (t, J=4.8 Hz, 4H), 2.56 (t, J=4.5 Hz, 4H), 2.29 (s,3H), 1.33 (s, 9H) ppm; MS (ES) 450.39 (M+H), 448.52 (M−H).

5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #359), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.99 (s,1H), 8.24 (d, J=9.3 Hz, 2H), 7.70 (br. s, 2H), 7.40 (d, J=8.4 Hz, 2H),7.05 (d, J=9.0 Hz, 2H), 6.87 (d, J=9.0 Hz, 2H), 4.78 (quint. J=6.0 Hz,1H), 3.13 (br. s, 4H), 2.85 (br. s, 4H), 2.53 (s, 3H), 1.32 (d, J=6.0Hz, 6H) ppm; MS (ES) 436.63 (M+H), 434.71 (M−H).

3-amino-1-(4-(iso-propoxy)phenyl)carbonyl-5-(4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #360), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 10.01 (s,1H), 8.22 (d, J=8.7 Hz, 2H), 7.56 (d, J=8.7 Hz, 2H), 7.02 (d, J=8.7 Hz,2H), 6.92 (d, J=8.7 Hz, 2H), 4.76 (quint. J=6.0 Hz, 1H), 3.09 (br. s,4H), 2.44 (br. s, 4H), 2.21 (s, 3H), 1.30 (d, J=6.0 Hz, 6H) ppm; MS (ES)436.63 (M+H).

5-amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #361), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.90 (s,1H), 8.26 (d, J=7.8 Hz, 2H), 7.63 (br. s, 2H), 7.41 (d, J=8.4 Hz, 2H),6.85 (d, J=8.4 Hz, 2H), 6.77 (d, J=8.7 Hz, 2H), 3.03-2.98 (m, 4H), 2.94(s, 3H), 2.93 (s, 3H), 2.50-2.42 (m, 4H), 2.21 (s, 3H) ppm; MS (ES)421.67 (M+H), 419.62 (M−H).

3-amino-1-(4-(dimethylamino)phenyl)carbonyl-5-(4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #362), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 10.12 (s, 1H),8.25 (d, J=9.0 Hz, 2H), 7.55 (d, J=8.1 Hz, 2H), 6.91 (d, J=9.0 Hz, 2H),6.72 (d, J=9.0 Hz, 2H), 5.95 (br. s, 2H), 3.12-3.04 (m, 4H), 3.03 (s,6H), 2.48-2.40 (m, 4H), 2.21 (s, 3H) ppm; MS (ES) 421.65 (M+H).

5-amino-1-(3-(dimethylamino)phenyl)carbonyl-3-[4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #363), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.97 (s,1H), 7.73 (br. s, 2H), 7.58 (s, 1H), 7.38 (d, J=8.7 Hz, 2H), 7.31 (d,J=7.5 Hz, 1H), 7.19 (t, J=8.4 Hz, 1H), 6.98 (d, J=8.4 Hz, 1H), 6.77 (d,J=8.7 Hz, 2H), 3.04-2.96 (m, 4H), 2.96 (s, 6H), 2.50-2.46 (m, 4H), 2.23(s, 3H) ppm; MS (ES) 421.79 (M+H), 419.62 (M−H).

3-amino-1-(3-(dimethylamino)phenyl)carbonyl-5-(4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #364), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 10.30 (s,1H), 7.30-7.25 (m, 2H), 7.20-7.15 (m, 4H), 6.90 (dm, J=8.4 Hz, 2H), 6.51(s, 2H), 3.36-3.30 (m, 4H), 2.94 (s, 6H), 2.53 (s, 3H), 2.50-2.46 (m,4H) ppm; MS (ES) 421.73 (M+H).

5-amino-1-(bicyclo[2.2.1]heptan-2-yl)carbonyl-3-[4-(4-methylpiperazin-1-yl)phenylamino]-1H-1,2,4-triazole(compound #365), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.67 (s,1H), 8.21 (br. s, 2H), 7.53 (d, J=8.7 Hz, 2H), 6.88 (d, J=8.7 Hz, 2H),3.12-3.04 (m, 4H), 2.45-2.37 (m, 4H), 2.30-2.26 (m, 1H), 2.20 (s, 3H),1.68-1.24 (m, 10H) ppm; MS (ES) 396.69 (M+H), 394.65 (M−H).

5-amino-1-(1H-indol-3-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #366), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 11.76 (br.s, 3H), 8.00-7.90 (m, 4H), 7.42 (d, J=7.2 Hz, 2H), 7.20-7.05 (m, 4H),4.10-4.06 (m, 2H), 3.06 (br. s, 2H), 2.52 (br. s, 4H), 1.70-1.62 (m, 4H)ppm; MS (ES) 432.10 (M+H), 430.25 (M−H).

5-amino-1-(benzo[b]thiophen-2-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #367), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.28 (s, 1H),8.70 (s, 1H), 8.15 (d, J=8.1 Hz, 1H), 8.11 (d, J=7.8 Hz, 1H), 7.87 (br.s, 2H), 7.63 (d, J=9.3 Hz, 2H), 7.56 (t, J=7.2 Hz, 1H), 7.48 (t, J=7.2Hz, 1H), 7.01 (d, J=9.0 Hz, 2H), 4.14 (t, J=5.7 Hz, 2H), 3.10 (br. s,2H), 2.86 (br. s, 4H), 1.86-1.75 (m, 4H) ppm; MS (ES) 449.10 (M+H),447.18 (M−H).

3-amino-1-(benzo[b]thiophen-2-yl)carbonyl-5-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #368), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.97 (br. s,1H), 8.81 (s, 1H), 8.10-8.02 (m, 2H), 7.64 (d, J=9.0 Hz, 2H), 7.60-7.45(m, 2H), 6.93 (d, J=9.9 Hz, 2H), 6.27 (br. s, 2H), 4.04 (t, J=5.7 Hz,2H), 2.77 (t, J=5.7 Hz, 2H), 2.60-2.50 (m, 4H), 1.70-1.62 (m, 4H) ppm;MS (ES) 449.05 (M+H), 447.23 (M−H).

5-amino-1-(benzo[b]thiophen-5-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #369), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.06 (br.s, 1H), 8.78 (s, 1H), 8.17-8.09 (m, 2H), 7.89 (d, J=4.5 Hz, 1H), 7.78(br. s, 2H), 7.62 (d, J=4.5 Hz, 1H), 7.42 (d, J=8.7 Hz, 2H), 7.78 (d,J=8.1 Hz, 2H), 3.97 (t, J=5.7 Hz, 2H), 2.77 (t, J=5.7 Hz, 2H), 2.53 (br.s, 4H), 1.68 (br. s, 4H) ppm; MS (ES) 449.05 (M+H), 447.26 (M−H).

5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #370), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.05 (br.s, 1H), 8.16 (d, J=8.7 Hz, 2H), 7.72 (br. s, 2H), 7.65 (s, 1H), 7.41 (d,J=9.0 Hz, 2H), 7.21 (s, 1H), 7.11 (d, J=8.4 Hz, 2H), 6.84 (s, 1H), 6.80(d, J=8.7 Hz, 2H), 4.30 (t, J=4.5 Hz, 2H), 4.17 (t, J=4.5 Hz, 2H), 1.41(s, 9H) ppm; MS (ES) 462.05 (M+H), 460.24 (M−H).

5-amino-1-(3-(tert-butoxy)phenyl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #371), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.07 (br. s,1H), 7.82 (d, J=7.2 Hz, 1H), 7.75 (br. s, 2H), 7.65 (s, 1H), 7.44 (t,J=7.5 Hz, 1H), 7.38 (d, J=8.7 Hz, 2H), 7.24 (d, J=7.5 Hz, 1H), 7.20 (s,1H), 6.86 (s, 1H), 6.75 (d, J=8.4 Hz, 2H), 4.49 (t, J=4.5 Hz, 2H), 4.14(t, J=4.5 Hz, 2H), 1.32 (s, 9H) ppm; MS (ES) 462.05 (M+H), 460.21 (M−H).

5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #372), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.05 (br. s,1H), 6.22 (d, J=9.0 Hz, 2H), 7.71 (br. s, 2H), 7.65 (s, 1H), 7.42 (d,J=9.3 Hz, 2H), 7.21 (s, 1H), 7.05 (d, J=8.7 Hz, 2H), 6.86 (s, 1H), 6.82(d, J=9.3 Hz, 2H), 4.78 (quint. J=6.0 Hz, 1H), 4.30 (t, J=5.1 Hz, 2H),4.16 (t, J=5.1 Hz, 2H), 1.32 (d, J=6.0 Hz, 6H) ppm; MS (ES) 448.06(M+H), 446.22 (M−H).

5-amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #373), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.00 (br. s,1H), 8.24 (d, J=9.0 Hz, 2H), 7.67 (s, 1H), 7.63 (br. s, 2H), 7.44 (d,J=8.7 Hz, 2H), 7.22 (s, 1H), 6.88 (s, 1H), 6.82 (d, J=9.3 Hz, 2H), 6.76(d, J=8.7 Hz, 2H), 4.31 (t, J=4.5 Hz, 2H), 4.16 (t, J=4.8 Hz, 2H), 3.04(s, 6H) ppm; MS (ES) 433.02 (M+H), 431.21 (M−H).

5-amino-1-(3-(dimethylamino)phenyl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #374), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.07 (br.s, 1H), 7.73 (s, 1H), 7.64 (br. s, 2H), 7.55 (s, 1H), 7.42 (d, J=8.4 Hz,2H), 7.36-7.32 (m, 2H), 7.20 (s, 1H), 6.98-6.90 (s, 1H), 6.75 (d, J=8.1Hz, 2H), 4.29 (t, J=4.5 Hz, 2H), 4.14 (t, J=4.5 Hz, 2H), 2.95 (s, 6H)ppm; MS (ES) 433.02 (M+H), 431.23 (M−H).

5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #375), pale brown solid; ¹H-NMR (DMSO-d₆, 300 MHz) 11.60 (br.s, 1H), 9.05 (br. s, 1H), 8.50 (s, 1H), 7.82 (d, J=8.4 Hz, 1H), 7.72(br. s, 2H), 7.69-7.62 (m, 2H), 7.45 (d, J=8.7 Hz, 2H), 7.22 (s, 1H),6.88 (s, 1H), 6.81 (d, J=8.4 Hz, 2H), 6.54 (s, 1H), 4.30 (t, J=4.5 Hz,2H), 4.15 (t, J=4.8 Hz, 2H) ppm; MS (ES) 429.00 (M+H), 427.18 (M−H).

3-amino-1-(1H-indol-6-yl)carbonyl-5-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #376), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 11.61 (br.s, 1H), 10.10 (br. s, 1H), 9.05 (s, 1H), 8.50 (s, 1H), 7.81 (m, 1H),7.72-7.63 (m, 2H), 7.45 (d, J=8.4 Hz, 2H), 7.21 (d, J=8.1 Hz, 1H), 6.92(d, J=9.0 Hz, 1H), 6.81 (d, J=8.4 Hz, 2H), 6.54 (br. s, 1H), 6.00 (br.s, 2H), 4.22 (t, J=4.5 Hz, 2H), 4.14 (t, J=4.8 Hz, 2H) ppm; MS (ES)429.00 (M+H), 427.17 (M−H).

5-amino-1-(benzo[b]thiophen-5-yl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #377), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.09 (br. s,1H), 8.77 (s, 1H), 8.18-8.06 (m, 3H), 7.89 (br. s, 1H), 7.78 (br. s,2H), 7.64 (br. s, 2H), 7.41 (d, J=8.4 Hz, 2H), 7.20 (s, 1H), 6.86 (s,1H), 6.77 (d, J=7.8 Hz, 2H), 4.29 (br. s, 2H), 4.14 (br. s, 2H) ppm; MS(ES) 445.95 (M+H), 444.15 (M−H).

3-amino-1-(benzo[b]thiophen-5-yl)carbonyl-5-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #378), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.09 (br. s,1H), 8.78 (s, 1H), 8.18-8.08 (m, 2H), 7.90 (d, J=5.4 Hz, 1H), 7.78 (br.s, 2H), 7.69 (s, 1H), 7.62 (d, J=5.4 Hz, 1H), 7.42 (d, J=9.0 Hz, 2H),7.22 (s, 1H), 6.89 (s, 1H), 6.77 (d, J=8.7 Hz, 2H), 4.30 (t, J=5.1 Hz,2H), 4.15 (t, J=5.1 Hz, 2H) ppm; MS (ES) 445.96 (M+H), 444.14 (M−H).

5-amino-1-(benzo[b]thiophen-2-yl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #379), yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.27 (br. s,1H), 8.69 (s, 1H), 8.15 (d, J=7.8 Hz, 1H), 8.10-8.08 (m, 1H), 7.86 (br.s, 2H), 7.71 (s, 1H), 7.61 (d, J=9.0 Hz, 2H), 7.56 (t, J=7.8 Hz, 1H),7.48 (t, J=8.1 Hz, 1H), 7.25 (s, 1H), 6.96 (d, J=8.4 Hz, 2H), 6.90 (s,1H), 4.34 (t, J=5.1 Hz, 2H), 4.23 (t, J=5.1 Hz, 2H) ppm; MS (ES) 445.95(M+H), 444.13 (M−H).

5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #380), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 10.05 (br.s, 1H), 9.09 (br. s, 1H), 8.17 (d, J=7.1 Hz, 2H), 7.71 (br. s, 2H), 7.45(d, J=6.9 Hz, 2H), 7.11 (d, J=7.1 Hz, 2H), 6.90 (d, J=7.1 Hz, 2H), 4.22(br. s, 2H), 3.53 (br. s, 4H), 3.10 (br. s, 2H), 1.97-1.88 (m, 4H), 1.41(s, 9H) ppm; MS (ES) 465.40 (M+H).

5-amino-1-(3-fluoro-4-methoxyphenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #381), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.17 (br.s, 1H), 8.20 (d, J=13.2 Hz, 1H), 8.07 (d, J=8.4 Hz, 1H), 7.77 (br. s,2H), 7.46 (d, J=8.7 Hz, 2H), 7.34 (t, J=8.4 Hz, 1H), 6.90 (d, J=8.7 Hz,2H), 4.21 (t, J=5.1 Hz, 2H), 3.95 (s, 3H), 3.60-3.50 (br. s, 2H),3.05-3.15 (m, 4H), 2.02-1.88 (m, 4H) ppm; MS (ES) 441.05 (M+H), 439.20(M−H).

5-amino-1-(4-(morpholin-4-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #382), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.10 (br.s, 1H), 8.23 (d, J=8.1 Hz, 2H), 7.68 (br. s, 2H), 7.48 (d, J=9.3 Hz,2H), 7.03 (d, J=8.4 Hz, 2H), 6.92 (t, J=8.1 Hz, 2H), 4.21 (br. s, 2H),3.75 (br. s, 4H), 3.33 (br. s, 4H), 3.30-3.20 (m, 2H), 3.20-3.05 (m,4H), 2.02-1.88 (m, 4H) ppm; MS (ES) 478.37 (M+H).

5-amino-1-(4-(4-methylpiperazin-1-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #383), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.11 (br.s, 1H), 8.25 (d, J=8.4 Hz, 2H), 7.71 (br. s, 2H), 7.48 (d, J=8.4 Hz,2H), 7.11 (d, J=8.4 Hz, 2H), 6.91 (t, J=8.7 Hz, 2H), 4.21-4.12 (m, 4H),3.55 (br. s, 4H), 3.14 (br. s, 4H), 2.87 (s, 3H), 2.53 (br. s, 4H),2.02-1.88 (m, 4H) ppm; MS (ES) 491.15 (M+H).

5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-[4-[2-((S)-3-fluoropyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #384), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.02 (br.s, 1H), 8.17 (d, J=8.1 Hz, 2H), 7.74 (br. s, 2H), 7.41 (d, J=8.4 Hz,2H), 7.11 (d, J=8.1 Hz, 2H), 6.82 (d, J=8.7 Hz, 2H), 3.99 (t, J=5.7 Hz,2H), 3.00-2.58 (m, 6H), 2.17-2.04 (m, 1H), 1.98-1.65 (m, 2H), 1.41 (s,9H) ppm; MS (ES) 483.35 (M+H), 481.47 (M−H).

5-amino-1-(4-(dimethylamino)phenyl)carbonyl-3-[4-[2-((S)-3-fluoropyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #385), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.97 (br.s, 1H), 8.25 (d, J=9.0 Hz, 2H), 7.63 (br. s, 2H), 7.45 (d, J=8.7 Hz,2H), 6.85 (d, J=8.7 Hz, 2H), 6.76 (d, J=9.0 Hz, 2H), 4.00 (t, J=5.7 Hz,2H), 3.05 (s, 6H), 3.00-2.70 (m, 6H), 2.26-2.06 (m, 1H), 1.98-1.78 (m,2H) ppm; MS (ES) 454.16 (M+H).

5-amino-1-(1,4-benzodioxan-6-yl)carbonyl-3-[4-[2-((S)-3-fluoropyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #386), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.03 (br.s, 1H), 7.82 (s, 1H), 7.79 (br. s, 1H), 7.71 (br. s, 2H), 7.42 (d, J=9.0Hz, 2H), 7.00 (d, J=8.7 Hz, 1H), 6.81 (d, J=8.4 Hz, 2H), 4.33 (d, J=6.3Hz, 4H), 3.99 (t, J=6.0 Hz, 2H), 2.98-2.68 (m, 6H), 2.26-2.06 (m, 1H),1.93-1.78 (m, 2H) ppm; MS (ES) 469.33 (M+H), 467.06 (M−H).

3-amino-1-(1,4-benzodioxan-6-yl)carbonyl-5-[4-[2-((S)-3-fluoropyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #387), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 10.01 (br.s, 1H), 8.18 (s, 1H), 7.84 (d, J=8.4 Hz, 1H), 7.79 (br. s, 1H), 7.63 (d,J=9.0 Hz, 2H), 7.92 (d, J=8.7 Hz, 2H), 6.06 (br. s, 2H), 4.33-4.30 (m,4H), 4.04 (t, J=5.4 Hz, 2H), 2.94-2.71 (m, 6H), 2.18-2.05 (m, 1H),1.92-1.76 (m, 2H) ppm; MS (ES) 469.19 (M+H), 466.86 (M−H).

5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-((S)-3-fluoropyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #388), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 11.59 (br.s, 1H), 9.01 (br. s, 1H), 8.51 (s, 1H), 7.83 (d, J=8.4 Hz, 1H), 7.71(br. s, 2H), 7.66-7.61 (m, 2H), 7.46 (d, J=8.4 Hz, 2H), 6.82 (d, J=8.1Hz, 2H), 6.54 (s, 1H), 3.97 (t, J=5.7 Hz, 2H), 2.94-2.65 (m, 6H),2.16-2.05 (m, 1H), 1.91-1.76 (m, 2H) ppm; MS (ES) 450.41 (M+H), 448.13(M−H).

3-amino-1-(1H-indol-6-yl)carbonyl-5-[4-[2-((S)-3-fluoropyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #389), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 11.54 (br.s, 1H), 9.02 (br. s, 1H), 8.44 (s, 1H), 7.84-7.80 (m, 1H), 7.68 (d,J=9.0 Hz, 2H), 7.46 (d, J=8.7 Hz, 1H), 6.94 (d, J=9.0 Hz, 2H), 6.82 (d,J=8.7 Hz, 1H), 6.54-6.52 (m, 1H), 6.00 (br. s, 2H), 4.97 (t, J=5.7 Hz,2H), 2.94-2.65 (m, 6H), 2.30-2.00 (m, 1H), 1.93-1.80 (m, 2H) ppm; MS(ES) 450.14 (M+H), 448.12 (M−H).

5-amino-1-(3,5-difluoro-4-methoxyphenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #390), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.10 (br.s, 1H), 8.03 (d, J=9.6 Hz, 2H), 7.80 (br. s, 2H), 7.39 (d, J=8.7 Hz,1H), 6.80 (d, J=8.7 Hz, 2H), 4.08 (s, 3H), 3.98 (t, J=5.7 Hz, 2H), 2.76(t, J=5.7 Hz, 2H), 2.49 (br. s, 4H), 1.67 (br. s, 4H) ppm; MS (ES)459.08 (M+H), 457.22 (M−H).

3-amino-1-(2,6-difluorophenyl)carbonyl-5-(1-methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole(compound #391), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 7.64-7.54(m, 1H), 7.23 (t, J=8.1 Hz, 2H), 6.50 (d, J=7.5 Hz, 1H), 6.02 (br. s,2H), 3.80-3.65 (m, 1H), 3.59-3.55 (m, 2H), 2.87 (s, 3H), 2.82-2.72 (m,3H), 2.04-2.01 (m, 2H), 1.87-1.78 (m, 2H) ppm; MS (ES) 401.03 (M+H).

5-amino-1-(2,6-difluorophenyl)carbonyl-3-(1-methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole(compound #392), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 7.74 (br. s,2H), 7.64-7.52 (m, 1H), 7.23 (t, J=8.7, 7.8 Hz, 2H), 6.50 (d, J=7.2 Hz,1H), 3.74-3.41 (m, 2H), 2.80 (s, 3H), 2.76-2.73 (m, 3H), 1.87-1.82 (m,2H), 1.50-1.36 (m, 2H) ppm; MS (ES) 401.03 (M+H).

5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3-(1-methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole(compound #393), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.12 (t,J=8.4, 7.5 Hz, 3H), 7.62 (br. s, 2H), 7.05 (d, J=8.4 Hz, 2H), 3.56-3.44(m, 2H), 2.84 (s, 3H), 2.85-2.78 (m, 3H), 2.05-1.90 (m, 2H), 1.60-1.45(m, 2H), 1.39 (s, 9H) ppm; MS (ES) 437.09 (M+H), 435.08 (M−H).

5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-(1-methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole(compound #394), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.18 (d,J=8.4 Hz, 2H), 7.82 (br. s, 1H), 7.60 (br. s, 2H), 6.98 (d, J=7.5 Hz,2H), 4.74 (quint. J=5.4 Hz, 1H), 3.58-3.40 (m, 2H), 2.84 (s, 3H),2.85-2.78 (m, 3H), 2.05-1.90 (m, 2H), 1.80-1.60 (m, 1H), 1.60-1.42 (m,1H), 1.29 (s, J=5.4 Hz, 6H) ppm; MS (ES) 423.06 (M+H), 421.06 (M−H).

5-amino-1-(4-(dimethylamino)phenyl)carbonyl-3-(1-methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole(compound #395), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.20 (d,J=8.7 Hz, 2H), 7.53 (br. s, 2H), 6.70 (d, J=8.7 Hz, 2H), 6.26 (d, J=7.2Hz, 1H), 3.52-3.42 (m, 2H), 3.01 (s, 6H), 2.88-2.78 (m, 3H), 2.84 (s,3H), 2.00-1.95 (m, 2H), 1.58-1.52 (m, 2H) ppm; MS (ES) 408.08 (M+H),406.22 (M−H).

3-amino-1-(4-(dimethylamino)phenyl)carbonyl-5-(1-methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole(compound #396), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.20 (d,J=9.0 Hz, 2H), 7.86 (d, J=7.5 Hz, 1H), 6.70 (d, J=8.7 Hz, 2H), 5.78 (br.s, 2H), 3.54-3.45 (m, 2H), 3.01 (s, 6H), 2.90-2.80 (m, 3H), 2.88 (s,3H), 2.05-1.96 (m, 2H), 1.76-1.50 (m, 2H) ppm; MS (ES) 408.08 (M+H),406.22 (M−H).

5-amino-1-(1,4-benzodioxan-6-yl)carbonyl-3-(1-methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole(compound #397), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 7.79 (s,1H), 7.62 (br. s, 2H), 6.93 (d, J=8.7 Hz, 2H), 6.37 (d, J=8.1 Hz, 1H),4.26 (dm, J=7.5 Hz, 4H), 3.55-3.44 (m, 2H), 2.88-2.80 (m, 3H), 2.84 (s,3H), 2.06-1.93 (m, 2H), 1.80-1.65 (m, 1H), 1.58-1.45 (m, 1H) ppm; MS(ES) 423.02 (M+H), 421.07 (M−H).

5-amino-1-(1H-indol-6-yl)carbonyl-3-(1-methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole(compound #398), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 11.50 (br.s, 1H), 8.42 (d, J=9.0 Hz, 1H), 7.87 (d, J=7.5 Hz, 1H), 7.58 (d, J=8.7Hz, 1H), 7.57 (br. s, 2H), 6.50 (s, 1H), 3.56-3.46 (m, 2H), 2.86-2.79(m, 3H), 2.83 (s, 3H), 2.10-1.97 (m, 2H), 1.80-1.68 (m, 1H), 1.60-1.46(m, 1H) ppm; MS (ES) 404.06 (M+H), 402.14 (M−H).

5-amino-1-(4-(morpholin-4-yl)phenyl)carbonyl-3-(1-methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole(compound #399), off-white solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.18 (d,J=8.4 Hz, 2H), 7.56 (br. s, 2H), 6.96 (d, J=8.7 Hz, 2H), 6.30 (d, J=7.2Hz, 1H), 3.72 (br. s, 4H), 3.50-3.40 (m, 2H), 2.88-2.80 (m, 3H), 2.85(s, 3H), 2.04-1.92 (m, 2H), 1.60-1.46 (m, 2H) ppm; MS (ES) 450.04 (M+H),448.21 (M−H).

5-amino-1-(4-(1,1-dioxo-thiomorpholin-4-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #400), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 9.01 (br.s, 1H), 8.23 (d, J=6.0 Hz, 2H), 7.68 (br. s, 2H), 7.44 (d, J=8.1 Hz,2H), 7.13 (d, J=8.1 Hz, 2H), 6.83 (d, J=6.0 Hz, 2H), 3.97 (br. s, 4H),3.15 (br. s, 6H), 2.85-2.75 (m, 2H), 2.52 (br. s, 4H), 1.68 (br. s, 4H)ppm; MS (ES) 526.04 (M+H), 524.13 (M−H).

5-amino-1-(4-(piperidin-1-yl)phenyl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole(compound #401), pale yellow solid; ¹H-NMR (DMSO-d₆, 300 MHz) 8.97 (br.s, 1H), 8.22 (d, J=9.0 Hz, 2H), 7.63 (br. s, 2H), 7.44 (d, J=9.0 Hz,2H), 6.98 (d, J=9.3 Hz, 1H), 6.84 (d, J=8.7 Hz, 2H), 3.99 (t, J=6.0 Hz,4H), 3.40 (br. s, 4H), 2.77 (t, J=5.7 Hz, 2H), 2.53 (br. s, 4H), 1.68(br. s, 4H), 1.60 (br. s, 6H) ppm; MS (ES) 476.95 (M+H), 474.62 (M−H).

5-amino-3-[3-chloro-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1-(3,5-dichlorophenyl)carbonyl-1H-1,2,4-triazole(compound #402); ¹H-NMR (DMSO-d₆) δ 8.18 (d, 1H), 7.90 (m, 3H), 7.19 (d,2H), 4.20 (t, 2H), 2.93 (m, 2H), 2.69 (m, 4H), 1.72 (s, 4H) ppm; MS (ES)496 (M+H).

5-amino-3-[N-(3-(4-(2-chloro-6-fluorophenyl)piperazin-1-yl)prop-1-yl)-N-((3-methylphenyl)carbonyl)amino]-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole(compound #403); mp 109-113° C.; ¹H-NMR (300 MHz, DMSO-d₆) δ 7.90 (br s,2H), 7.40-7.08 (m, 10H), 6.92 (d, J=7.8 Hz, 1H), 3.81 (m, 2H), 3.55 (brs, 2H), 2.50-2.20 (m, 14H), 1.74 (m, 2H); IR (ATR) 2813, 1663, 1549,1440 cm⁻¹; ESI MS m/z 605 [C₃₂H₃₆ClFN₇O₂+H]⁺; HPLC (Method 1) 91.9%(AUC), t_(R)=11.56 min.

3-amino-5-[3-(4-(2-chloro-6-fluorophenyl)piperazin-1-yl)prop-1-yl]amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole(compound #404); mp 86-92° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 8.13 (m, 1H),7.87-7.82 (m, 2H), 7.40-7.30 (m, 4H), 7.21 (m, 1H), 5.84 (br s, 2H),3.59 (br s, 2H), 3.39 (m, 2H), 2.37-2.30 (m, 13H), 1.74 (m, 2H); ¹³C NMR(75 MHz, DMSO-d₆) δ 164.6, 160.4, 158.2, 156.4, 135.3, 134.0, 133.9,131.4, 130.9, 128.6, 128.4, 128.3, 126.0, 125.6, 123.8, 122.0, 121.7,112.8, 122.5, 54.2, 51.1, 50.6, 50.3, 40.3, 23.8, 19.3; IR (ATR) 2814,1669, 1630, 1650, 1573 cm⁻¹; ESI MS m/z 486 [C₂₄H₂₉ClFN₇O+H]⁺; HPLC(Method 1) 96.7% (AUC), t_(R)=9.55 min.

-   5-amino-3-[3-(4-(2-chloro-6-fluorophenyl)piperazin-1-yl)prop-1-yl]amino-1-(3-methylphenyl)carbonyl-1H-1,2,4-triazole    (compound #405); mp 62-69° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 7.90 (m,    2H), 7.63 (br s, 2H), 7.40-7.32 (m, 4H), 7.22 (m, 1H), 6.29 (m, 1H),    3.57 (m, 2H), 3.03 (m, 2H), 2.40-2.20 (m, 8H), 2.36 (s, 3H), 1.63    (m, 2H); ¹³C NMR (75 MHz, DMSO-d₆) δ 166.7, 163.5, 162.5, 160.2,    158.4, 137.3, 135.9, 133.7, 133.3, 133.1, 131.1, 130.5, 130.3,    130.1, 128.8, 128.0, 127.9, 126.8, 125.9, 123.9, 123.7, 114.8,    114.5, 55.9, 53.0, 52.8, 52.3, 26.6, 22.0; IR (ATR) 2938, 1672,    1587, 1347 cm⁻¹; ESI MS m/z 486 [C₂₄H₂₉ClFN₇O+H]⁺; HPLC (Method 1)    95.8% (AUC), t_(R)=9.91 min.

All compounds of the invention which exist in free base or acid form canbe converted to their pharmaceutically acceptable salts by treatmentwith the appropriate inorganic or organic base or acid by methods knownto one of ordinary skill in the art. Salts of the compounds of theinvention can be converted to their free base or acid form by standardtechniques known to one skilled in the art.

Testing of the Compounds of the Invention

The compounds of the invention were tested in the following assay fortheir ability to inhibit Axl activity.

Phospho-Akt in-Cell Western Assay

Reagents and Buffers:

-   Cell culture plate: 96 well assay plate (Corning 3610), white, clear    bottom, tissue-culture treated.-   Cells: Hela cells.-   Starvation medium: For Axl stimulation: 0.5% FCS (fetal calf serum)    in DMEM, plus Axl/Fc (extracellular domain of AXL fused to    immunoglobulin Fc region) (R&D, 154-AL) 500 ng/mL.-   For EGF (epidermal growth factor) stimulation: 0.5% FCS in DMEM    (Dulbecco's modified Eagles medium).-   Poly-L-Lysine 0.01% solution (the working solution): 10 μg/ml,    dilute In PBS (phosphate buffered saline).-   Axl antibody cross-linking:    -   1^(st): Mouse anti-Axl (R&D, MAB154).    -   2^(nd): Biotin-SP-conjugated AffiniPure goat anti-mouse IgG        (H+L) (Jackson ImmunoResearch #115-065-003).-   Fixing buffer: 4% formaldehyde in PBS.-   Wash buffer: 0.1% TritonX-100 in PBS.-   Quenching buffer: 3% H₂O₂, 0.1% Azide in wash buffer, Azide and    hydrogen peroxide (H₂O₂) are added fresh.-   Blocking buffer: 5% BSA in TBST (tris buffered saline plus 0.1%    Tween 20).-   Primary antibody: Rabbit anti-human Phospho-Akt antibody (Cell    Signaling 9271): 1×250 diluted in blocking buffer.-   Secondary antibody: HRP (horse radish peroxidase)-conjugated Goat    anti-Rabbit secondary, stock solution: Jackson ImmunoResearch (Goat    anti-Rabbit HRP, #111-035-144) 1:1 diluted in glycerol, store at    −20° C. The working solution: 1×2000 dilution of stock in blocking    buffer.-   Chemiluminescent working solution (Pierce, 37030): SuperSignal ELISA    (enzyme linked immunosorbant assay) Pico Chemiluminescent substrate.-   Crystal Violet solution: Stock: 2.5% Crystal violet in methanol,    filtered and kept at ambient temperature. The working solution:    dilute the stock 1:20 with PBS immediately before use.-   10% SDS: working solution: 5% SDS (sodium dodecylsulfate), diluted    in PBS    Methods:    Day 1:

A 96 well TC (tissue culture treated) plate was coated with 10 μg/mLpoly-L-Lysine at 37° C. for 30 min, washed twice with PBS, and air-driedfor 5 minutes before cells were added. Hela cells were seeded at 10,000cells/well and the cells were starved in 100 μL starvation mediumcontaining Axl/Fc for 24 hrs.

Day 2:

The cells were pre-treated with test compounds by adding 100 μL of 2×test compound to the starvation medium on the cells. The cells wereincubated at 37° C. for 1 hr before stimulation.

The cells were stimulated by Axl-antibody cross-linking as follows: A5×1^(st)/2^(nd) Axl antibody mixture was made (37.5 μg/mL 1^(st)/100μg/mL 2^(nd)) in starvation medium and nutated at 4° C. with thoroughmixing for 1-2 hours for clustering. The resulting mix was warmed to 37°C. 50 μL of 5× Axl 1^(st)/2^(nd) of antibody cluster was added to thecells and the cells were incubated at 37° C. for 5 min.

After 5 minutes stimulation, the plate was flicked to remove medium andthe plate was tapped onto paper towels. Formaldehyde (4.0% in PBS, 100μL) was added to fix the cells and the cells were incubated at ambienttemperature for 20 min without shaking.

The cells were washed with a plate washer buffer to remove theformaldehyde solution. The plate was flicked to removed excess washbuffer and tapped onto paper towels. Quenching buffer (100 μL) was addedto each well and the cells were incubated at ambient temperature for 20minutes without shaking.

The cells were washed with a plate washer buffer to remove the quenchingbuffer. Blocking buffer (100 μL) was added and the cells were incubatedat ambient temperature for at least an hour with gentle shaking.

The cells were washed with a plate washer buffer and diluted primaryantibody (50 μL) was added to each well (blocking buffer was added tothe negative control wells instead). The plates were incubated overnightat 4° C. with gentle shaking.

Day 3:

The wash buffer was removed, diluted secondary antibody (100 μL) wasadded, and the cells were incubated at ambient temperature for 1 hourwith gentle shaking. During the incubation, the chemiluminescent reagentwas brought to ambient temperature.

The secondary antibody was removed by washing the cells 1× with washbuffer, 1× with PBS by plate washer. The PBS was removed from the plateand the chemiluminescent reagent (80 μL: 40 μL A and 40 μL B) was addedto each well at ambient temperature.

The resulting chemiluminescence was read with a Luminomitor within 10minutes to minimize changes in signal intensity. After reading thechemiluminescence, the cells were washed 1× with wash buffer and 1× withPBS by plate washer. The plate was tapped onto paper towels to removeexcess liquid from wells and air-dried at ambient temperature for 5minutes.

Crystal Violet working solution (60 μL) was added to each well and thecells were incubated at ambient temperature for 30 min. The crystalviolet solution was removed, and the wells were rinsed with PBS, thenwashed 3× with PBS (200 μL) for 5 minutes each.

5% SDS solution (70 μL) was added to each well and the cells wereincubated on a shaker for 30 min at ambient temperature.

The absorbance was read at 590 nM on a Wallac photospec. The 590 nMreadings indicated the relative cell number in each well. This relativecell number was then used to normalize each luminescence reading.

The results of the ability of the compounds of the invention to inhibitAxl activity, when tested in the above assay, are shown in the followingTables 1-10 wherein the level of activity (i.e., the IC₅₀) for eachcompound is indicated in each Table. The compound numbers in the Tablesreferred to the compounds disclosed herein as being prepared by themethods disclosed herein:

TABLE 1

Cpd # Compound Name R^(1b) R^(1c) R^(1d) R⁴ R^(3b) R^(3c) R^(3d) R^(3e)R^(3f) IC₅₀ 168 5-amino-1-(3-(iso- propoxy)phenyl) carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy] phenylamino]- 1H-1,2,4-triazole

—H —H —H —H

—H —H —H A 169 5-amino-1-(3-(iso- propoxy)phenyl)carbonyl- 3-[4-[2-(morpholin-4- yl)ethoxy]phenylamino]- 1H-1,2,4- triazole

—H —H —H —H

—H —H —H A 170 5-amino-1-(3-(iso- propoxy)phenyl) carbonyl-3- [3-(1,3-oxazol-5-yl) phenylamino]- 1H-1,2,4- triazole —H

—H —H —H

—H —H —H B  94 5-amino-1-(2- (chloro)phenyl) carbonyl-3- (1,4-benzodioxan-6-yl) amino-1H-1,2,4- triazole

—H —H —H —H —Cl —H —H D  95 5-amino-1-(4- (chloro)phenyl)carbonyl-3-(1,4- benzodioxan-6-yl) amino-1H-1,2,4- triazole

—H —H —Cl —H —H —H —H B  96 5-amino-3-(1,4- benzodioxan-6-yl)amino-1-(3- (methyl)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —H —CH₃ —H —H —H B  97 5-amino-3-(1,4- benzodioxan-6-yl)amino-1-(2- (methyl)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —H —H —CH₃ —H —H C  98 5-amino-3-(1,4- benzodioxan-6-yl)amino-1-(3- (methoxy)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —H —OCH₃ —H —H —H B  99 5-amino-3-(1,4- benzodioxan-6-yl)amino-1-(2- (fluoro)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —H —H —F —H —H C 100 5-amino-3-(1,4- benzodioxan-6- yl)amino-1-(4-(fluoro)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —F —H —H —H —H D 101 5-amino-1-(3- (chloro)phenyl)carbonyl-3-(1,4- benzodioxan-6-yl) amino-1H-1,2,4- triazole

—H —H —H —Cl —H —H —H B 102 5-amino-3-(1,4- benzodioxan-6-yl)amino-1-(4- (methyloxy)phenyl) carbonyl-1H- 1,2,4- triazole

—H —H —OCH₃ —H —H —H —H B (Ia-15) 5-amino-3-[3- (hydroxy)phenylamino]-1-(4- (methyl)phenyl) carbonyl-1H-1,2,4- triazole —H —OH —H—H —CH₃ —H —H —H —H C (Ia-4) 5-amino-3-[4- (hydroxy) phenylamino]-1-(4-(methyl)phenyl) carbonyl-1H-1,2,4- triazole —OH —H —H —H —CH₃ —H —H —H—H D 104 5-amino-3-(1,4- benzodioxan-6- yl)amino-1-(4- (methyl)phenyl)carbonyl-1H-1,2,4- triazole

—H —H —CH₃ —H —H —H —H B 105 5-amino-3-(1,4- benzodioxan-6-yl)amino-1-(3- (fluoro)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —H —F —H —H —H D 106 5-amino-3-(1,4- benzodioxan-6- yl)amino-1-(2-(methyloxy)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —H —H —OCH₃ —H —H D (Ia-6) 5-amino-3-[3- (hydroxy)phenyl-amino]-1-(2- (methyl)phenyl) carbonyl-1H-1,2,4- triazole —H —OH —H —H —H—H —CH₃ —H —H D (Ia-7) 5-amino-3[3- (hydroxy) phenylamino]-1-(3-(methyl)phenyl) carbonyl-1H-1,2,4- triazole —H —OH —H —H —H —CH₃ —H —H—H B (Ia-5) 5-amino-3-[3- (cyanomethoxy) phenylamino]-1-(4-(methyl)phenyl) carbonyl-1H-1,2,4- triazole —H —OCH₂CN —H —H —CH₃ —H —H—H —H D (Ia-10) 5-amino-3-[4- (benzyloxy) phenylamino]-1- (4-(iso-propoxy)phenyl) carbonyl-1H-1,2,4- triazole —OCH₂—Ph —H —H —H

—H —H —H —H D 109 1-(4-(acetoxy)phenyl) carbonyl-5- amino-3-(1,4-benzodioxan-6- yl)amino-1H- 1,2,4-triazole

—H —H —OC(O)CH₃ —H —H —H —H B 110 1-(3-(acetoxy)phenyl) carbonyl-5-amino-3-(1,4- benzodioxan-6- yl)amino-1H- 1,2,4-triazole

—H —H —H —OC(O)CH₃ —H —H —H B (Ia-8) 5-amino-3-[3- (cyanomethoxy)phenylamino]-1-(2- (methyl)phenyl) carbonyl-1H-1,2,4- triazole —H—OCH₂CN —H —H —H —H —CH₃ —H —H D (Ia-9) 5-amino-3-[3- (cyanomethoxy)phenylamino]-1-(3- (methyl)phenyl) carbonyl-1H-1,2,4- triazole —H—OCH₂CN —H —H —H —CH₃ —H —H —H D (Ia-17) 5-amino-3-[3- (benzyloxy)phenylamino]-1- (3-(iso- propoxy)phenyl) carbonyl-1H-1,2,4- triazole —H—OCH₂—Ph —H —H —H

—H —H —H D 111 5-amino-3-[4-(iso- propoxy) phenylamino]-1- (4-(iso-propoxy)phenyl) carbonyl-1H-1,2,4- triazole

H —H —H

—H —H —H —H B 112 5-amino-3-(1,4- benzodioxan-6- yl)amino-1-(3-(iso-propoxy)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —H

—H —H —H B 113 5-amino-3-(1,4- benzodioxan-6- yl)amino-1-(4-(iso-propoxy)phenyl) carbonyl-1H-1,2,4- triazole

—H —H

—H —H —H —H B 114 5-amino-1-(4- ethoxyphenyl) carbonyl-3-(1,4-benzodioxan-6-yl) amino-1H-1,2,4- triazole

—H —H —OCH₂CH₃ —H —H —H —H B (Ia-16) 5-amino-3-[3- (hydroxy)phenylamino]-1- (3-(iso- propoxy)phenyl) carbonyl-1H-1,2,4- triazole —H—OH —H —H —H

—H —H —H B (Ia-13) 5-amino-3-[3- (hydroxy) phenylamino]- 1-(4-(iso-propoxy)phenyl) carbonyl-1H-1,2,4- triazole —H —OH —H —H

—H —H —H —H B (Ia-25) 5-amino-3-[3- (benzyloxy) phenylamino]-1-(4-(iso-propoxy)phenyl) carbonyl-1H-1,2,4- triazole —H —OCH₂—Ph —H —H

—H —H —H —H D 116 5-amino-3-[3- (cyclopentoxy) phenylamino]-1-(4-(iso-propoxy) phenyl)carbonyl-1H- 1,2,4-triazole —H

—H —H

—H —H —H —H D (Ia-11) 5-amino-3-[4- (hydroxy) phenylamino]-1-(4-(iso-propoxy)phenyl) carbonyl-1H-1,2,4- triazole —OH —H —H —H

—H —H —H —H B 117 5-amino-1-(4-(iso- propoxy)phenyl) carbonyl-3-[4-(methoxy) phenylamino]-1H-1,2,4- triazole —OCH₃ —H —H —H

—H —H —H —H B 118 5-amino-3-[4-(ethoxy) phenylamino]- 1-(4-(iso-propoxy)phenyl)carbonyl- 1H-1,2,4-triazole —OCH₂CH₃ —H —H —H

—H —H —H —H B 119 1-(2-(acetoxy) phenyl)carbonyl-5- amino-3-(1,4-benzodioxan-6- yl)amino-1H- 1,2,4-triazole

—H —H —H —H

—H —H B 120 5-amino-1-(4- (cyclopentoxy) phenylcarbonyl-3-(1,4-benzodioxan- 6-yl)amino-1H- 1,2,4-triazole

—H —H

—H —H —H —H D 121 5-amino-1-(4-(iso- propoxy)phenyl) carbonyl-3-[3-(methoxy) phenylamino]-1H-1,2,4- triazole —H —OCH₃ —H —H

—H —H —H —H B 122 5-amino-3-[3-(iso- propoxy)phenylamino)-1-(4-iso-propoxy)phenyl) carbonyl-1H-1,2,4- triazole —H

—H —H

—H —H —H —H B 123 5-amino-3-[4- (fluoro)phenylamino]-1-(4-(methyl)phenyl) carbonyl-1H- 1,2,4-triazole —F —H —H —H —CH₃ —H —H —H—H C 124 5-amino-3-[3- (fluoro)phenylamino]-1- (4-(methyl)phenyl)carbonyl-1H- 1,2,4-triazole —H —F —H —H —CH₃ —H —H —H —H C (Ia-26)5-amino-3-[3-[2- (morpholin-4- yl)ethoxy] phenylamino]-1-phenylcarbonyl-1H- 1,2,4-triazole —H

—H —H —H —H —H —H —H D (Ia-27) 5-amino-1-(3- (methyl)phenylcarbonyl-3-[3-[2- (morpholin-4- yl)ethoxy] phenylamino]-1H-1,2,4-triazole —H

—H —H —H —CH₃ —H —H —H B (Ia-22) 5-amino-1-(4-(iso- propoxy)phenylcarbonyl-3-[3-[2- (morpholin-4- yl)ethoxy] phenylamino]-1H-1,2,4-triazole —H

—H —H

—H —H —H —H B 125 5-amino-3-[3- (ethoxy)phenylamino]- 1-(4-(iso-propoxy)phenyl) carbonyl- 1H-1,2,4-triazole —H —OCH₂CH₃ —H —H

—H —H —H —H B 126 5-amino-3-(1,4- benzodioxan-6- yl)amino-1-[4-(methoxy- carbonylmethoxy) phenyl)- carbonyl-1H- 1,2,4-triazole

—H —H

—H —H —H —H B 127 5-amino-1-(3- (cyclopentoxy)phenyl) carbonyl-3-(1,4-benzodioxan- 6-yl)amino-1H- 1,2,4-triazole

—H —H —H

—H —H —H B 128 5-amino-1-(3- (ethoxy)phenyl) carbonyl-3-(1,4-benzodioxan-6-yl) amino-1H-1,2,4- triazole

—H —H —H —OCH₂CH₃ —H —H —H D 129 5-amino-3-[2- (fluoro)phenylamino]-1-(4-(methyl) phenyl)carbonyl-1H- 1,2,4-triazole —H —H —F —H —CH₃ —H —H —H—H D 131 5-amino-3-[4- (methyl)phenylamino]- 1-(4-(methyl)phenyl)carbonyl-1H- 1,2,4-triazole —CH₃ —H —H —H —CH₃ —H —H —H —H D 1325-amino-3-[4- (methoxy) phenylamino]-1-(4- (methyl) phenyl)carbonyl-1H-1,2,4- triazole —OCH₃ —H —H —H —CH₃ —H —H —H —H B 133 5-amino-3-[3-(methyl)phenylamino]- 1-(4-(methyl) phenyl)carbonyl-1H- 1,2,4-triazole—H —CH₃ —H —H —CH₃ —H —H —H —H B 134 5-amino-3-[3- (methoxy)phenylamino]-1-(4- (methyl)phenyl) carbonyl-1H-1,2,4- triazole —H —OCH₃—H —H —CH₃ —H —H —H —H B 135 5-amino-1-(4-(iso- propoxy)phenyl)carbonyl-3-[3- (methoxy- carbonylmethoxy) phenyl- amino]-1H-1,2,4-triazole —H

—H —H

—H —H —H —H B (Ia-23) 5-amino-1-(4-(iso- propoxy)phenyl) carbonyl-3-[3-(piperidin-1-yl) phenylamino]-1H- 1,2,4-triazole —H

—H —H

—H —H —H —H B (Ia-24) 5-amino-3-[3-[2- (1,3-dioxolan-2- yl)ethoxy]phenylamino]-1-(4-(iso- propoxy) phenyl)carbonyl- 1H-1,2,4- triazole —H

—H —H

—H —H —H —H B 137 5-amino-1-(4- (methyl)phenyl) carbonyl-3- phenylamino-1H-1,2,4-triazole —H —H —H —H —CH₃ —H —H —H —H D 138 5-amino-3-(1,4-benzodioxan-6- yl)amino-1-[3- (methoxy- carbonylmethoxy) phenyl)carbonyl- 1H-1,2,4-triazole

—H —H —H

—H —H —H B 139 5-amino-1-(4-(iso- propoxy)phenyl) carbonyl-3-[3-(2,2,2-trifluoroethoxy) phenylamino]-1H- 1,2,4-triazole —H —OCH₂CF₃ —H —H

—H —H —H —H D (Ia-12) 5-amino-3-[4- (cyanomethoxy) phenylamino]-1-(4-(iso-propoxy) phenyl)carbonyl-1H- 1,2,4-triazole —OCH₂CN —H —H —H

—H —H —H —H B (Ia-21) 5-amino-3-[3- (cyanomethoxy) phenylamino]-1-(4-(iso-propoxy) phenyl)carbonyl-1H- 1,2,4-triazole —H —OCH₂CN —H —H

—H —H —H —H B 142 5-amino-1-(4- (benzyloxy)phenyl) carbonyl-3-(1,4-benzodioxan- 6-yl)amino-1H-1,2,4- triazole

—H —H —OCH₂Ph —H —H —H —H B 143 5-amino-3-[2- (methoxy)phenylamino]-1-(4- (methyl) phenyl)carbonyl- 1H-1,2,4- triazole —H —H—OCH₃ —H —CH₃ —H —H —H —H D 144 5-amino-3-[2- (methyl)phenylamino]-1-(4-(methyl) phenyl)carbonyl-1H- 1,2,4-triazole —H —H —CH₃ —H —CH₃ —H—H —H —H D 145 5-amino-3-[-[2- (hydroxyl)ethoxy] phenylamino]-1-(3-(methyl)phenyl) carbonyl-1H-1,2,4- triazole —H

—H —H —CH₃ —H —H —H —H B 146 5-amino-3-[3- (methyl-aminocarbonylmethoxy)- phenylamino]-1-(3- (methyl)phenyl)carbonyl-1H-1,2,4- triazole —H

—H —H —H —CH₃ —H —H —H B 147 5-amino-3-[3- (methoxy- carbonylmethoxy)phenylamino]- 1-(3-(methyl)phenyl) carbonyl- 1H-1,2,4-triazole —H

—H —H —H —CH₃ —H —H —H B 148 5-amino-3-[3-(N- (2,2-dimethyl-1,3-dioxolan-4- yl)methyl) aminocarbonylmethoxy)- phenylamino]-1-(3-(methyl)phenyl) carbonyl-1H-1,2,4- triazole —H

—H —H —H —CH₃ —H —H —H B 149 5-amino-3-(1,4- benzodioxan-6-yl)amino-1-[4-[2- (morpholin-4- yl)ethoxy]phenyl] carbonyl-1H-1,2,4-triazole

—H —H

—H —H —H —H B 150 5-amino-3-(1,4- benzodioxan-6- yl)amino-1-[3-[2-(morpholin-4- yl)ethoxy]phenyl] carbonyl-1H-1,2,4- triazole

—H —H —H

—H —H —H D 151 5-amino-3-[4- (cyclopentoxy) phenylamino]-1-(4-(iso-propoxy) phenyl)carbonyl-1H- 1,2,4-triazole

—H —H —H

—H —H —H —H D 152 5-amino-1-(4-(iso- propoxy)phenyl)carbonyl-3-[4-(2,2,2- trifluoroethoxy) phenylamino]-1H- 1,2,4-triazole—OCH₂CF₃ —H —H —H

—H —H —H —H D 153 5-amino-3-[3-(N-(2,3- dihydroxypropyl) amino)carbonyl-methoxy]- phenylamino-1-(3- (methyl) phenyl)carbonyl-1H-1,2,4- triazole—H

—H —H —H —CH₃ —H —H —H B 156 5-amino-1-(3- (benzyloxy)phenyl)carbonyl-3-(1,4- benzodioxan- 6-yl)amino-1H-1,2,4- triazole

—H —H —H —OCH₂Ph —H —H —H C 157 5-amino-1-(4-(iso- propoxy)phenyl)carbonyl-3-[4- (methoxy- carbonylmethoxy)phenyl-amino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H B 158 5-amino-3-[4-[2- (1,3-dioxolan-2- yl)ethoxy]phenylamino]-1-(4-(iso- propoxy) phenyl)carbonyl-1H-1,2,4- triazole

—H —H —H

—H —H —H —H B 159 5-amino-1-(4-(iso- propoxy) phenylcarbonyl-3-[4-[2-(morpholin-4- yl)ethoxy] phenylamino]-1H-1,2,4- triazole

—H —H —H

—H —H —H —H A 162 5-amino-3- (1,4-benzodioxan-6- yl)amino-1-(4-(hydroxy) phenyl)carbonyl-1H-1,2,4- triazole

—H —H —OH —H —H —H —H B 163 5-amino-1-(4-(iso- propoxy)phenylcarbonyl-3-[4-[2- (piperidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 165 5-amino-3-[3- [cyclohexyl- aminocarbonylmethoxy]-phenylamino]-1-(3- (methyl)phenyl) carbonyl-1H-1,2,4- triazole —H

—H —H —H —CH₃ —H —H —H D 166 5-amino-3- (1,4-benzodioxan-6-yl)amino-1-(3- (hydroxy) phenyl)carbonyl-1H-1,2,4- triazole

—H —H —H —OH —H —H —H B 210 5-amino-1-[3- [2-(1,3-dioxolan-2- yl)ethoxy]phenylcarbonyl-3-(1,4- benzodioxan- 6-yl)amino-1H-1,2,4- triazole

—H —H —H

—H —H —H B 211 5-amino-3-[2- (hydroxyl) phenylamino]-1-(4- methylphenyl)carbonyl-1H-1,2,4- triazole —H —H —OH —H —CH₃ —H —H —H —H D 2125-amino-1-(3- methylphenyl) carbonyl-3-[3-[(2- methoxyethoxy) methoxy]phenylamino]- 1H-1,2,4-triazole —H

—H —H —H —CH₃ —H —H —H B 214 5-amino-1-[4-[2- (1,3-dioxolan-2-yl)ethoxy] phenylcarbonyl-3-(1,4- benzodioxan-6- yl)amino-1H-1,2,4-triazole

—H —H

—H —H —H —H B 216 5-amino-3-(3- methoxymethoxy) phenylamino-1-(3-methylphenyl) carbonyl-1H-1,2,4- triazole —H

—H —H —H —CH₃ —H —H —H D 217 5-amino-3-(4- chlorophenyl)amino-1-(4-chlorophenyl) carbonyl-1H-1,2,4- triazole —Cl —H —H —H —Cl —H —H —H—H D 218 5-amino-3-(4- bromophenyl)amino-1- (4-chlorophenyl)carbonyl-1H-1,2,4- triazole —Br —H —H —H —Cl —H —H —H —H B 2215-amino-1-(3- methylphenyl) carbonyl-3-[(3-tert- butoxycarbonyl-methoxy)phenyl]amino- 1H-1,2,4-triazole —H

—H —H —H —CH₃ —H —H —H B 223 5-amino-1-(3- methylphenyl)carbonyl-3-[3-[2- (tetrahydropyran-2- yl) ethoxyaminocarbonyl] methoxy]phenylamino- 1H-1,2,4-triazole —H

—H —H —H —CH₃ —H —H —H B 224 5-amino-3-(3- hydroxycarbonylmethoxy)phenylamino- 1-(3-methylphenyl) carbonyl-1H- 1,2,4-triazole —H

—H —H —H —CH₃ —H —H —H D 225 5-amino-3-[3-((2- hydroxyethyl)aminocarbonylmethoxy) phenyl]amino-1-(3- methylphenyl)carbonyl-1H-1,2,4- triazole —H

—H —H —H —CH₃ —H —H —H B 226 5-amino-3- (1,4-benzodioxan-6-yl)amino-1-[4-[2- (piperidin-1- yl)ethoxy] phenylcarbonyl-1H-1,2,4-triazole

—H —H

—H —H —H —H B (Ia-18) 5-amino-1-(3- methylphenyl) carbonyl-3-[3-[2-(4-morpholinyl) ethylaminocarbonyl- methoxy] phenyl]amino-1H-1,2,4-triazole —H

—H —H —H —CH₃ —H —H —H B (Ia-19) 5-amino-1-(3- methylphenyl)carbonyl-3-[3-(N-tert- butoxycarbonyl) piperazin-4- ylcarbonylmethoxy)phenyl]amino- 1H-1,2,4-triazole —H

—H —H —H —CH₃ —H —H —H D 228 5-amino-3-(1,4- benzodioxan-6-yl)amino-1-(3-(2,2,2- trifluoroethoxy) phenyl)carbonyl-1H-1,2,4-triazole

—H —H —H —OCH₂CF₃ —H —H —H D (Ia-20) 5-amino-1-(3- methylphenyl)carbonyl-3-[3- (piperazin-4- ylcarbonylmethoxy) phenyl]amino-1H-1,2,4-triazole —H

—H —H —H —CH₃ —H —H —H B 230 5-amino-3-(1,4- benzodioxan-6-yl)amino-1-(4-(2,2,2- trifluoroethoxy)phenyl) carbonyl-1H-1,2,4-triazole

—H —H —OCH₂CF₃ —H —H —H —H D 231 5-amino-1-(3- aminocarbonylmethoxy)phenylcarbonyl- 3-(1,4-benzodioxan- 6-yl)amino- 1H-1,2,4-triazole

—H —H —H

—H —H —H D 232 5-amino-3-(1,4- benzodioxan-6- yl)amino-1-(4-iso-propylphenyl) carbonyl-1H-1,2,4- triazole

—H —H —CH(CH₃)₂ —H —H —H —H B 234 5-amino-1-(3,4- dimethylphenyl)carbonyl-3-(1,4- benzodioxan-6-yl) amino-1H-1,2,4- triazole

—H —H —CH₃ —CH₃ —H —H —H B 237 5-amino-3-(1,4- benzodioxan-6-yl)amino-1-(4- thiomethylphenyl) carbonyl-1H-1,2,4- triazole

—H —H —SCH₃ —H —H —H —H B 240 5-amino-3-(1,4- benzodioxan-6-yl)amino-1-(4- nitrophenyl)carbonyl- 1H-1,2,4-triazole

—H —H —NO₂ —H —H —H —H D 242 5-amino-3-(1,4- benzodioxan-6- yl)amino-1-[(4-fluoro-3- methyl)phenyl] carbonyl-1H-1,2,4- triazole

—H —H —F —CH₃ —H —H —H D 243 5-amino-1- (4-aminophenyl)carbonyl-3-(1,4-benzodioxan-6- yl)amino-1H- 1,2,4-triazole

—H —H —NH₂ —H —H —H —H B 235 5-amino-1-(3- methylphenyl) carbonyl-3-[3-(methylsulfonyl methoxy)phenyl]amino- 1H-1,2,4-triazole —H

—H —H —H —CH₃ —H —H —H B 244 5-amino-3-(1,4- benzodioxan-6-yl)amino-1-[(4- trifluoromethyl) phenyl]carbonyl-1H- 1,2,4-triazole

—H —H —CF₃ —H —H —H —H D 245 5-amino-1-(4- cyanophenyl)carbonyl-3-(1,4-benzodioxan- 6-yl)amino-1H- 1,2,4-triazole

—H —H —CN —H —H —H —H D 246 1-[(4-acetylamino)phenyl] carbonyl-5-amino-3-(1,4- benzodioxan-6- yl)amino-1H-1,2,4-triazole

—H —H

—H —H —H —H B 247 5-amino-1-[(4- dimethylamino)phenyl] carbonyl-3-(1,4-benzodioxan- 6-yl)amino-1H- 1,2,4-triazole

—H —H —N(CH₃)₂ —H —H —H —H B 248 5-amino-3-(1,4- benzodioxan-6-yl)amino-1-[(4- methylsulfonyl) phenyl]carbonyl-1H- 1,2,4-triazole

—H —H —SO₂CH₃ —H —H —H —H D 249 5-amino-1-[(3-chloro-4- methyl)phenyl]carbonyl-3-(1,4- benzodioxan-6-yl) amino-1H-1,2,4- triazole

—H —H —CH₃ —Cl —H —H —H D 257 5-amino-3-(1,4- benzodioxan-6-yl)amino-1-(3-methyl-4- methoxy)phenyl- carbonyl-1H-1,2,4- triazole

—H —H —OCH₃ —CH₃ —H —H —H B 258 5-amino-3-(1,4- benzodioxan-6-yl)amino-1-(3- methyl-4-iso- propoxy) phenylcarbonyl- 1H-1,2,4- triazole

—H —H

—CH₃ —H —H —H B  48 5-amino-1-(4-(iso- propoxy)phenyl) carbonyl-3-(4-(morpholin-4- yl)phenylamino]-1H- 1,2,4-triazole

—H —H —H

—H —H —H —H A  50 5-amino-3-[4-[2- (piperidin-1- yl)ethoxy]phenylamino]-1-(4-(tert- butoxy) phenyl)carbonyl- 1H-1,2,4- triazole

—H —H —H

—H —H —H —H A  51 5-amino-1-(4-(iso- propyl)phenyl) carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy] phenylamino]- 1H-1,2,4-triazole

—H —H —H —CH(CH₃)₂ —H —H —H —H A  52 5-amino-1-(4-(iso- propyl)phenyl)carbonyl-3-(4- (morpholin-4-yl) phenylamino]-1H- 1,2,4-triazole

—H —H —H —CH(CH₃)₂ —H —H —H —H A  53 5-amino-1-(4- (methyl)phenyl)carbonyl-3-[4-[2- (piperidin-1-yl)ethoxy] phenylamino]-1H-1,2,4-triazole

—H —H —H —CH₃ —H —H —H —H A  54 5-amino-1-(4- (methyl)phenyl)carbonyl-3-(4- (morpholin-4-yl) phenylamino)-1H- 1,2,4-triazole

—H —H —H —CH₃ —H —H —H —H A  55 5-amino-3-[4-(iso- propoxy)phenylamino]-1-(4- (methyl)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —H —CH₃ —H —H —H —H A  57 5-amino-3-(4- (morpholin-4-yl)phenylamino)-1- (4-(tert- butoxy)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —H

—H —H —H —H A  59 5-amino-1-(3- (methyl)phenyl) carbonyl-3-[4-[2-(piperidin-1-yl) ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H —H —H —CH₃ —H —H —H A  60 5-amino-1-(4-(iso- propoxy)phenylcarbonyl-3-[4-[2- (thiomorpholin-4- yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H —H

—H —H —H —H A  61 5-amino-1-(3- (methyl) phenylcarbonyl-3-[4-[2-(thiomorpholin-4- yl)ethoxy] phenylamino]-1H-1,2,4- triazole

—H —H —H —H —CH₃ —H —H —H B  62 5-amino-1-(4- (cyclohexyl)phenyl)carbonyl-3-[4-[2- (piperidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H B  67 5-amino-1-(3- (hydroxy)phenyl) carbonyl-3-(4-(morpholin-4-yl) phenylamino)-1H- 1,2,4-triazole

—H —H —H —H —OH —H —H —H B  70 5-amino-1-(4- (aminosulfonyl)phenyl)carbonyl-3-(4- (morpholin-4- yl)phenylamino)-1H- 1,2,4-triazole

—H —H —H —SO₂NH₂ —H —H —H —H D  71 5-amino-3-[4- (iso-propoxy)phenylamino]-1-(3- (nitro)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —H —H —NO₂ —H —H —H B  72 5-amino-3-(4- (morpholin-4-yl)phenylamino)-1-(3- (nitro)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —H —H —NO₂ —H —H —H B  73 5-amino-1-(3- (hydroxy)phenyl)carbonyl-3-[4-(iso- propoxy) phenylamino]-1H-1,2,4- triazole

—H —H —H —H —OH —H —H —H B  74 5-amino-1-(3- (chloro)phenyl)carbonyl-3-(4- (morpholin-4-yl) phenylamino)-1H- 1,2,4-triazole

—H —H —H —H —Cl —H —H —H B  76 5-amino-1-(3- (chloro)phenyl)carbonyl-3-[4-(iso- propoxy) phenylamino]-1H-1,2,4- triazole

—H —H —H —H —Cl —H —H —H D  77 5-amino-3-[4-(iso- propoxy)phenylamino]-1-[4-[2- (piperidin-1- yl)ethoxy] phenyl)carbonyl-1H-1,2,4- triazole

—H —H —H

—H —H —H —H B  79 5-amino-1-(3- (methoxycarbonyl) phenyl)carbonyl-3-[4-[2-(piperidin-1- yl)ethoxy] phenylamino]-1H-1,2,4- triazole

—H —H —H —H —CO₂CH₃ —H —H —H B  80 5-amino-1-(3- (methoxy)phenyl)carbonyl-3-[4-[2- (piperidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H —H —OCH₃ —H —H —H A  81 5-amino-1-(3- (methoxy)phenyl)carbonyl-3-(4- (morpholin-4-yl) phenylamino)-1H- 1,2,4-triazole

—H —H —H —H —OCH₃ —H —H —H B  82 5-amino-3-[4-[2- (dimethylamino)ethoxy]phenyl- amino]-1-(4- (methyl)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —H —CH₃ —H —H —H —H  83 5-amino-3-[4-[2- (dimethylamino)ethoxy]phenylamino]- 1-(4-(tert-butoxy) phenyl)carbonyl-1H-1,2,4-triazole

—H —H H

—H —H —H —H A  84 5-amino-3-[4-[2- (dimethylamino) propoxy]phenyl-amino]-1-(4-(iso- propoxy)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —H

—H —H —H —H A  85 5-amino-3-[4-[2- (dimethylamino) ethoxy]phenyl-amino]-1-(4-(iso- propoxy)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —H

—H —H —H —H A  87 5-amino-3-[4-[2- (dimethylamino) ethoxy]phenylamino]-1-(4- (dimethylamino) phenyl)carbonyl-1H- 1,2,4-triazole

—H —H —H —N(CH₃)₂ —H —H —H —H A  88 5-amino-1-(4- (dimethylamino)phenyl)carbonyl-3- [4-[2- (dimethylamino) propoxy]phenyl-amino]-1H-1,2,4-triazole

—H —H —H —N(CH₃)₂ —H —H —H —H A  89 5-amino-3-[4-[2- (dimethylamino)propoxy]phenyl- amino]-1-(4-(tert- butoxy)phenyl) carbonyl-1H-1,2,4-triazole

—H —H —H

—H —H —H —H B  91 5-amino-3-[4-[3- (dimethylamino) propoxy]phenyl-amino]-1-(4- (methyl)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —H —CH₃ —H —H —H —H B (Ia-2) 5-amino-1-(4-(iso- propoxy)phenyl)carbonyl-3-[4-[2- (pyrrolidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H A  26 5-amino-1-(4-(iso- propoxy)phenyl) carbonyl-3-[4-(piperidin-1-yl) phenylamino]-1H- 1,2,4-triazole

—H —H —H

—H —H —H —H B  13 5-amino-1-(1,3- benzodioxol-5- yl)carbonyl-3-[4-[2-(piperidin-1- yl)ethoxy] phenylamino]-1H-1,2,4- triazole

—H —H —H

—H —H —H A  21 5-amino-1-(3,4- (dimethoxy)phenyl) carbonyl-3-[4-[2-(piperidin-1-yl) ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H —H —OCH₃ —OCH₃ —H —H —H A  19 5-amino-1-(3,5- (dimethoxy)phenyl)carbonyl-3-[4-[2- (piperidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H —H —OCH₃ —H —OCH₃ —H A 239 5-amino-3-(1,4- benzodioxan-6-yl)amino-1-(3,5- dimethylphenyl) carbonyl-1H-1,2,4- triazole

—H —H —H —CH₃ —H —CH₃ —H B  11 5-amino-1-(3- (dimethylamino)phenyl)carbonyl-3- [4-[2-(piperidin-1- yl)ethoxy] phenylamino]-1H-1,2,4-triazole

—H —H —H —H —N(CH₃)₂ —H —H —H A  2 5-amino-1-(4- (dimethylamino)phenyl)carbonyl-3- [4-[2-(piperidin-1- yl)ethoxy] phenylamino]-1H-1,2,4-triazole

—H —H —H —N(CH₃)₂ —H —H —H —H A  16 5-amino-1- (1,3-benzodioxol-5-yl)carbonyl-3- [4-[2-(pyrrolidin-1- yl)ethoxy] phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H A  9 5-amino-1-(3- methylphenyl) carbonyl-3-[4-[2-(pyrrolidin-1-yl) ethoxy] phenylamino]- 1H-1,2,4-triazole

—H —H —H —H —CH₃ —H —H —H A  22 5-amino-1-(3,5- (dimethoxy)phenyl)carbonyl-3-[4-[2- (pyrrolidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H —H —OCH₃ —H —OCH₃ —H A  12 5-amino-1-(4- methylphenyl)carbonyl-3-[4-[2- (pyrrolidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H —CH₃ —H —H —H —H A  17 5-amino-1-(1,4- benzodioxan-6-yl)carbonyl-3-[4-[2- (pyrrolidin-1- yl)ethoxy] phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H A  1 5-amino-3-[4-[2- (pyrrolidin-1- yl)ethoxy]phenylamino]-1-(4-(tert- butoxy)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —H

—H —H —H —H A  14 5-amino-1-(3- (methoxy)phenyl) carbonyl-3-[4-[2-(pyrrolidin-1-yl) ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H —H —H —OCH₃ —H —H —H A  4 5-amino-1-(4- (dimethylamino)phenyl)carbonyl-3- [4-[2-(pyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H —H —N(CH₃)₂ —H —H —H —H A 197 5-amino-1-(3- (dimethylamino)phenyl)carbonyl-3- [4-[2-(pyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H —H —H —N(CH₃)₂ —H —H —H D 198 5-amino-1-(3,4- (dimethoxy)phenyl)carbonyl-3-[4-[2- (pyrrolidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H —OCH₃ —OCH₃ —H —H —H D  18 5-amino-3-[4-[2- (pyrrolidin-1-yl)ethoxy] phenylamino]-1-(3-(tert- butoxy)phenyl) carbonyl-1H-1,2,4-triazole

—H —H —H —H

—H —H —H A  7 5-amino-3-[4-[2- (pyrrolidin-1- yl)ethoxy]phenylamino]-1-(3- (trifluoromethoxy) phenyl)carbonyl- 1H-1,2,4-triazole

—H —H —H —H —OCF₃ —H —H —H A  23 5-amino-3-[4-[2- (pyrrolidin-1-yl)ethoxy] phenylamino]-1-(4- (trifluoromethoxy) phenyl)carbonyl-1H-1,2,4-triazole

—H —H —H —OCF₃ —H —H —H —H A  15 5-amino-3-[4-[3- (pyrrolidin-1-yl)propoxy] phenylamino]-1-(4-(tert- butoxy)phenyl) carbonyl-1H-1,2,4-triazole

—H —H —H

—H —H —H —H A  24 5-amino-3-[4-[3- (pyrrolidin-1- yl)propoxy]phenylamino]-1-(3-(tert- butoxy)phenyl) carbonyl-1H-1,2,4- triazole

—H —H —H —H

—H —H —H A  10 5-amino-1-(4-(iso- propoxy)phenyl) carbonyl-3-[4-[3-(pyrrolidin-1- yl)propoxy] phenylamino]-1H-1,2,4- triazole

—H —H —H

—H —H —H —H A  8 5-amino-1-(4- (dimethylamino) phenyl)carbonyl-3-[4-[3-(pyrrolidn-1- yl)propoxy] phenylamino]-1H-1,2,4- triazole

—H —H —H —N(CH₃)₂ —H —H —H —H A  20 5-amino-1-(3- (dimethylamino)phenyl)carbonyl-3- [4-[3-(pyrrolidin-1- yl)propoxy]phenylamino]-1H-1,2,4- triazole

—H —H —H —H —N(CH₃)₂ —H —H —H A 262 5-amino-3-[4-[2- (pyrrolidin-1-yl)ethoxy]-3- fluorophenyl] amino-1-[4- (morpholin-4-yl)phenyl]carbonyl-1H- 1,2,4-triazole

—F —H —H

—H —H —H —H A 263 5-amino-1-(4-(tert- butyl)phenyl) carbonyl-3-[3-(1,3-oxazol-5-yl) phenylamino]-1H-1,2,4- triazole —H

—H —H —C(CH₃)₃ —H —H —H —H B 264 5-amino-1-(4-(tert- butoxy)phenyl)carbonyl-3-[3-(1,3- oxazol-5-yl) phenylamino]-1H-1,2,4- triazole —H

—H —H —OC(CH₃)₃ —H —H —H —H B 266 5-amino-1-(4-(tert- butyl)phenyl)carbonyl-3-[4-[2- (morpholin-4- yl)ethoxy] phenylamino]-1H-1,2,4-triazole

—H —H —H —C(CH₃)₃ —H —H —H —H A 267 5-amino-1-(4-(tert- butoxy)phenyl)carbonyl-3-[4-[2- (morpholin-4- yl)ethoxy] phenylamino]-1H-1,2,4-triazole

—H —H —H —OC(CH₃)₃ —H —H —H —H A 268 5-amino-1-(4- (imidazol-1-yl)phenyl) carbonyl-3-[4-[2- (pyrrolidin-1-yl)ethoxy] phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 269 5-amino-1-(4- (phenoxy)phenyl) carbonyl-3-[4-[2-(pyrrolidin-1-yl) ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 270 5-amino-1-(4-(tert- butoxycarbonylamino) phenyl)-carbonyl-3-[4-[2- (pyrrolidin-1- yl)ethoxy] phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 272 5-amino-1-(4-(tert- butoxy)phenyl) carbonyl-3-[4-[2-(pyrrolidin-1- yl)ethoxy]phenyl] [methyl]amino-1H- 1,2,4-triazole

—H —H —CH₃ —OC(CH₃)₃ —H —H —H —H D 277 5-amino-1-(4- (phenyl)phenyl)carbonyl-3-[4-[2- (pyrrolidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 278 5-amino-1-[4-((tert- butoxycarbonyl) aminomethyl)-phenyl]carbonyl- 3-[4-[2-(pyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H —H

—H —H —H —H A 280 5-amino-1-(4- (1,2,3-thiadiazol-4- yl)phenyl)carbonyl-3-[4-[2- (pyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 282 5-amino-1-(4- (pyrrol-1- yl)phenyl) carbonyl-3-[4-[2-(pyrrolidin-1-yl) ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 286 5-amino-1-(4- (methylamino) phenyl)carbonyl-3-[4-[2-(pyrrolidin-1- yl)ethoxy] phenylamino]-1H-1,2,4- triazole

—H —H —H —N(CH₃)H —H —H —H —H A 287 5-amino-1-(4- (methylthio)phenyl)carbonyl-3-[4-[2- (pyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H —S—CH₃ —H —H —H —H A 289 5-amino-1-(2,6- difluorophenyl)carbonyl-3-[4-[2- (pyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H —H —H —F —H —F D 290 5-amino-1-(4-(tert- butylcarbonylamino)phenyl)carbonyl- 3-[4-[2-(pyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H —H

H —H —H —H C 291 5-amino-1-(4-(tert- butoxy)phenyl) carbonyl-3-[4-(pyrrolidin-1-yl) phenylamino]-1H- 1,2,4-triazole

—H —H —H —OC(CH₃)₃ —H —H —H —H D 293 5-amino-1-(4-(iso- propoxy)phenyl)carbonyl-3-[4- (pyrrolidin-1-yl) phenylamino]-1H- 1,2,4-triazole

—H —H —H

—H —H —H —H B 297 5-amino-1-(4-(tert- butyl)phenyl) carbonyl-3-[4-(pyrrolidin-1-yl) phenylamino]-1H- 1,2,4-triazole

—H —H —H —C(CH₃)₃ —H —H —H —H D 299 5-amino-1-(4- (dimethylamino)phenyl)carbonyl-3- [4-(pyrrolidin-1-yl) phenylamino]-1H- 1,2,4-triazole

—H —H —H —N(CH₃)₂ —H —H —H —H B 300 5-amino-1-(4- (methyl)phenyl)carbonyl-3-[4- (pyrrolidin-1- yl)phenylamino]-1H- 1,2,4-triazole

—H —H —H —CH₃ —H —H —H —H B 302 5-amino-1-(4-(tert- butyl)phenyl)carbonyl-3-[4-[2- (pyrrolidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H —C(CH₃)₃ —H —H —H —H A 305 5-amino-1-(4-(tert- butoxy)phenyl)carbonyl-3-[3-fluoro- 4-[2-(pyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—F —H —H —OC(CH₃)₃ —H —H —H —H A 306 5-amino-1-(4- (1,2,3-thiadiazol-4-yl)phenyl)carbonyl- 3-[3-fluoro-4-[2- (pyrrolidin-1-yl)ethoxy]phenylamino]- 1H-1,2,4-triazole

—F —H —H

—H —H —H —H A 307 5-amino-1-(4-(iso- propoxy)phenyl)carbonyl-3-[3-fluoro- 4-[2-(pyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—F —H —H

—H —H —H —H A 308 5-amino-1- (phenyl)carbonyl-3-[3- fluoro-4-[2-(pyrrolidin-1- yl)ethoxy] phenylamino]-1H-1,2,4- triazole

—F —H —H —H —H —H —H —H A 310 5-amino-1-(3- (thiazol-2-yl)phenyl)carbonyl- 3-[4-[2- (pyrrolidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 311 5-amino-1-(4-(thien-2- yl)phenyl) carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy] phenylamino]- 1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 313 5-amino-1-(3-(thien-2- yl)phenyl) carbonyl-3-[4-[2-(pyrrolidin-1-yl) ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H —H —H

—H —H —H A 314 5-amino-1-(4-(thien-3- yl)phenyl) carbonyl-3-[4-[2-(pyrrolidin-1-yl) ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 315 5-amino-1-(4-(tert- butyl)phenyl)carbonyl-3-[3-methoxy- 4-[2-(pyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—OCH₃ —H —H —C(CH₃)₃ —H —H —H —H A 316 5-amino-1-(4-(iso- propoxy)phenyl)carbonyl-3-[3- methoxy-4- [2-(pyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—OCH₃ —H —H

—H —H —H —H A 317 5-amino-1-(4-(tert- butoxy)phenyl) carbonyl-3-[3-methoxy-4- [2-(pyrrolidin-1- yl)ethoxy] phenylamino]-1H-1,2,4- triazole

—OCH₃ —H —H —OC(CH₃)₃ —H —H —H —H A 319 5-amino-1-(4-(1,2,3-thiadiazol-4- yl)phenyl) carbonyl-3- [3-methoxy-4-[2-(pyrrolidin-1- yl)ethoxy] phenylamino]-1H-1,2,4- triazole

—OCH₃ —H —H

—H —H —H —H A 320 5-amino-1-(4-(tert- butyl)phenyl) carbonyl-3-[4-[2-(azepan-1-yl) ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H —H —C(CH₃)₃ —H —H —H —H A 321 5-amino-1-(4-(iso- propoxy)phenyl)carbonyl-3-[4-[2- (azepan-1-yl) ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 322 5-amino-1-(4-(tert- butoxy)phenyl) carbonyl-3-[4-[2-(azepan-1-yl) ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H —H —OC(CH₃)₃ —H —H —H —H A 324 5-amino-1-(4- (1,2,3-thiadiazol-4-yl)phenyl) carbonyl-3-[4-[2-(azepan- 1-yl)ethoxy] phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 327 5-amino-1-(4- (morpholin-4- yl)phenyl)carbonyl-3-[4-[2- (isoindolin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 328 5-amino-1-(4-(iso- propoxy)phenyl) carbonyl-3-[4-[2-(isoindolin-1-yl) ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H —H

—H —H —H —H B 329 5-amino-1-(4-(tert- butoxy)phenyl) carbonyl-3-[4-[2-(isoindolin-1-yl) ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H —H —OC(CH₃)₃ —H —H —H —H B 331 5-amino-1-(3- (morpholin-4-yl)phenyl) carbonyl-3-[4-[2- (pyrrolidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H —H

—H —H —H A 332 5-amino-1-[4-(2- (morpholin-4- yl)ethoxy)phenyl]carbonyl-3-[4-[2- (pyrrolidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 333 5-amino-1-(4-(iso- propoxy)phenyl) carbonyl-3-(phenylamino)- 1H-1,2,4-triazole —H —H —H —H

—H —H —H —H B 334 5-amino-1-(4- (1,2,3-thiadiazol-4- yl)phenyl)carbonyl-3- (phenylamino)- 1H-1,2,4-triazole —H —H —H —H

—H —H —H —H D 335 5-amino-1- (4-(morpholin-4- yl)phenyl) carbonyl-3-(phenylamino)- 1H-1,2,4-triazole —H —H —H —H

—H —H —H —H D 336 5-amino-1- (3-(morpholin-4- yl)phenyl) carbonyl-3-(phenylamino)- 1H-1,2,4-triazole —H —H —H —H —H

—H —H —H C 337 5-amino-1-(4-(iso- propoxy)phenyl) carbonyl-3-[4-[2-(pyrrolidin-2-on-1- yl)ethoxy] phenylamino]-1H-1,2,4- triazole

—H —H —H

—H —H —H —H A 338 5-amino-1- (4-(1,2,3-thiadiazol-4- yl)phenyl)carbonyl-3-[4-[2- (pyrrolidin-2-on-1- yl)ethoxy] phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H B 339 5-amino-1-(4- (morpholin-4- yl)phenyl)carbonyl-3-[4-[2- (pyrrolidin-2-on-1- yl)ethoxy] phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H B 340 5-amino-1-(3- (morpholin-4- yl)phenyl)carbonyl-3-[4-[2- (pyrrolidin-2-on-1- yl)ethoxy] phenylamino]-1H-1,2,4-triazole

—H —H —H —H

—H —H —H B 341 5-amino-1-(4-(tert- butoxy) phenyl)carbonyl-3-(phenylamino)- 1H-1,2,4-triazole —H —H —H —H —OC(CH₃)₃ —H —H —H —H B 3425-amino-1-(4-(tert- butoxy)phenyl) carbonyl-3-[4-[2- (pyrrolidin-2-on-1-yl)ethoxy] phenylamino]-1H-1,2,4- triazole

—H —H —H —OC(CH₃)₃ —H —H —H —H A 343 5-amino-1-(4- (morpholin-4-yl)phenyl)carbonyl-3- [3-methoxy-4- [2-(pyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—OCH₃ —H —H

—H —H —H —H A 344 5-amino-1-(3- (morpholin-4- yl)phenyl)carbonyl-3-[3-methoxy-4- [2-(pyrrolidin-1- yl)ethoxy] phenylamino]-1H-1,2,4-triazole

—OCH₃ —H —H —H

—H —H —H A 357 5-amino-1-(4-(tert- butoxy)phenyl) carbonyl-3-[4-(4-methyl- piperazin-1-yl) phenylamino]- 1H-1,2,4-triazole

—H —H —H —OC(CH₃)₃ —H —H —H —H A 358 5-amino-1-(3-(tert- butoxy)phenyl)carbonyl-3-[4-(4- methylpiperazin-1-yl) phenylamino]- 1H-1,2,4-triazole

—H —H —H —H —OC(CH₃)₃ —H —H —H A 359 5-amino-1-(4-(iso- propoxy)phenyl)carbonyl-3-[4-(4- methylpiperazin- 1-yl)phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 361 5-amino-1-(4- (dimethylamino) phenyl)carbonyl-3-[4-(4- methylpiperazin-1- yl)phenylamino]- 1H-1,2,4-triazole

—H —H —H —N(CH₃)₂ —H —H —H —H A 363 5-amino-1-(3- (dimethylamino)phenyl)carbonyl-3- [4-(4- methylpiperazin-1- yl)phenylamino]-1H-1,2,4-triazole

—H —H —H —H —N(CH₃)₂ —H —H —H A 370 5-amino-1-(4-(tert- butoxy)phenyl)carbonyl-3-[4-[2- (imidazol-1-yl) ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H —H —OC(CH₃)₃ —H —H —H —H A 371 5-amino-1-(3-(tert- butoxy)phenyl)carbonyl-3-[4-[2- (imidazol-1-yl) ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H —H —H —OC(CH₃)₃ —H —H —H B 372 5-amino-1-(4-(iso- propoxy)phenyl)carbonyl-3-[4-[2- (imidazol-1-yl) ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 373 5-amino-1-(4- (dimethylamino) phenyl)carbonyl-3-[4-[2-(imidazol-1- yl)ethoxy] phenylamino]-1H-1,2,4- triazole

—H —H —H —N(CH₃)₂ —H —H —H —H A 374 5-amino-1-(3- (dimethylamino)phenyl)carbonyl-3- [4-[2-(imidazol-1- yl)ethoxy] phenylamino]-1H-1,2,4-triazole

—H —H —H —H —N(CH₃)₂ —H —H —H B 380 5-amino-1- (4-(tert- butoxy)phenyl)carbonyl-3-[4-[2- (pyrrolidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H —H —OC(CH₃)₃ —H —H —H A 381 5-amino-1-(3-fluoro-4-methoxyphenyl) carbonyl-3-[4-[2- (pyrrolidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H —OCH₃ —F —H —H —H A 382 5-amino-1-(4- (morpholin-4- yl)phenyl)carbonyl-3-[4-[2- (pyrrolidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 383 5-amino-1-(4-(4- methylpiperazin-1- yl)phenyl)carbonyl-3-[4-[2- (pyrrolidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 384 5-amino-1-(4-(tert- butoxy)phenyl)carbonyl-3-[4-[2-((S)- 3-fluoropyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H —H —OC(CH₃)₃ —H —H —H —H A 385 5-amino-1-(4- (dimethylamino)phenyl)carbonyl-3- [4-[2-((S)-3- fluoropyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H —H —N(CH₃)₂ —H —H —H —H A 390 5-amino-1-(3,5- difluoro-4-methoxyphenyl) carbonyl-3-[4-[2- (pyrrolidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H —OCH₃ —F —H —F —H A 400 5-amino-1-(4- (1,1-dioxo-thiomorpholin-4-yl) phenyl)carbonyl- 3-[4-[2-(pyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H —H

—H —H —H —H A 401 5-amino-1-(4- (piperidin-1- yl)phenyl)carbonyl-3-[4-[2- (pyrrolidin-1-yl) ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H —H

—H —H —H —H A 402 5-amino-3-[3- chloro-4-[2-(pyrrolidin- 1-yl)ethoxy]phenylamino]-1-(3,5- dichlorophenyl) carbonyl-1H-1,2,4- triazole

—Cl —H —H —H —Cl —H —Cl —H D IC₅₀ activity: A = <1 μM B = 1 to 10 μM C= >10 to 20 μM D = >20 μM

TABLE 2

Cpd Compound # Name R^(1b) R^(1c) R^(1d) R^(3b) R^(3c) R^(3d) R^(3e)IC₅₀ 92 3-amino-5-(1,4- benzodioxan-6- yl)amino- 1-phenylcarbo- nyl-1H-1,2,4-triazole

—H —H —H —H —H B 155 3-amino-1-(3- (benzyloxy) phenyl)carbo- nyl-5-(1,4-benzodioxan- 6-yl)amino- 1H-1,2,4- triazole

—H —H —OCH₂Ph —H —H D 164 3-amino-5-[3- [cyclohexyl- aminocarbonyl-methoxy] phenylamino]- 1-(3-(methyl) phenyl) carbonyl-1H- 1,2,4-triazole—H

—H —H —CH₃ —H —H D 209 3-amino-1-[3- [2-(1,3-di- oxolan- 2-yl)ethoxy]phenylcarbo- nyl-5-(1,4- benzodioxan-6- yl)amino-1H- 1,2,4-triazole

—H —H

—H —H D 213 3-amino- 1-[4-[2-(1,3- dioxolan-2- yl)ethoxy) phenyl-carbonyl-5- (1,4-benzo- dioxan-6- yl)amino-1H- 1,2,4-triazole

—H

—H —H —H D 233 3-amino-5-(1,4- benzodioxan-6- yl)amino-1-(4- iso-propylphenyl) carbonyl-1H- 1,2,4-triazole

—H —CH(CH₃)₂ —H —H —H D 236 3-amino-1-(3,4- dimethyl- phenyl) carbonyl-5-(1,4-benzo- dioxan- 6-yl)amino-1H- 1,2,4-triazole

—H —CH₃ —CH₃ —H —H D 238 3-amino-5-(1,4- benzodioxan-6- yl)amino-1-(4-thiomethyl- phenyl)carbo- nyl-1H-1,2,4- triazole

—H —SCH₃ —H —H —H D 241 3-amino-5-(1,4- benzodioxan-6- yl)amino-1-[(4-fluoro-3- methyl)phenyl] carbonyl-1H- 1,2,4-triazole

—H —F —CH₃ —H —H D 47 3-amino-1- (4-(iso-pro- poxy)phenyl)carbonyl-5-[4- [2- (piperidin-1-yl) ethoxy] phenylamino]- 1H-1,2,4-triazole

—H

—H —H —H D 49 3-amino-1-(4- (iso-propoxy) phenyl) carbonyl-5-(4-(morpho- lin-4-yl)phenyl- amino]-1H- 1,2,4-triazole

—H —H

—H —H —H D 56 3-amino-5-[4- (iso-propoxy) phenylamino]- 1-(4-(methyl)phenyl) carbonyl-1H- 1,2,4-triazole

—H —H —CH₃ —H —H —H D 58 3-amino-5-(4- (morpho- lin-4-yl)phenyl-amino)-1-(4- (tert- butoxy)phenyl) carbonyl-1H- 1,2,4-triazole

—H —H

—H —H —H D 75 3-amino-1-(3- (chloro)phenyl) carbonyl- 5-(4-(morpho-lin-4-yl) phenylamino)- 1H- 1,2,4-triazole

—H —H —H —Cl —H —H D 191 3-amino-1-(4- iso-propoxy- phenyl) carbonyl-5-[4-[2-(pyrroli- din-1-yl)eth- oxy)phenyl- amino]-1H- 1,2,4-triazole

—H —H

—H —H —H B 192 3-amino-1-(4- (iso-propoxy) phenyl) carbonyl-5-[4-(piperidin- 1-yl)phenyl- amino]- 1H-1,2,4-tri- azole

—H —H

—H —H —H C 292 3-amino-1-(4- (tert- butoxy)phenyl) carbonyl-5-(4-(pyrroli- din-1-yl)phenyl- amino]-1H- 1,2,4-triazole

—H —H —OC(CH₃)₃ —H —H —H D 294 3-amino-1- (4-(iso-pro- poxy)phenyl)carbonyl-5- (4-(pyrrolidin- 1-yl)phenyl- amino]-1H- 1,2,4-triazole

—H —H

—H —H —H D 298 3-amino-1-(4- (tert-butyl) phenyl) carbonyl-5-[4-(pyrrolidin- 1-yl)phenyl- amino]-1H- 1,2,4-triazole

—H —H —C(CH₃)₃ —H —H —H D 301 3-amino-1-(4- methylphenyl) carbonyl-5-(4-(pyrrolidin-1- yl)phenyl- amino]-1H- 1,2,4-triazole

—H —H —CH₃ —H —H —H D 303 3-amino-1-(4- (tert-butyl) phenyl)carbonyl-5-[4- [2-(pyrroli- din-1-yl) ethoxy]phenyl- amino]-1H-1,2,4-triazole

—H —H —C(CH₃)₃ —H —H —H B 304 3-amino-1-(4- (morpholin-4- yl)phenyl)carbonyl-5-[3- fluoro-4-[2- (pyrrolidin- 1-yl) ethoxy)phenyl- amino]-1H-1,2,4-triazole

—F —H

—H —H —H C 360 3-amino-1-(4- (iso-propoxy) phenyl)carbo- nyl-5-(4-(4-methylpipe- razin-1-yl) phenylamino]- 1H-1,2,4- triazole

—H —H

—H —H —H B 362 3-amino-1-(4- (dimethyl- amino)phenyl) carbonyl-5-(4-(4-methyl- piperazin-1-yl) phenyl- amino]-1H- 1,2,4-triazole

—H —H —N(CH₃)₂ —H —H —H B 364 3-amino-1-(3- (dimethyl- amino)phenyl)carbonyl-5- (4-(4-methyl- piperazin- 1-yl)phenyl- amino]-1H-1,2,4-triazole

—H —H —H —N(CH₃) —H —H B IC₅₀ activity: A = <1 μM B = 1 to 10 μM C = >10to 20 μM D = >20 μM

TABLE 3

Cpd # Compound Name R^(1b) R^(1c) R^(1d) R^(3g) IC₅₀ 1715-amino-1-(3-(iso-propoxy)pyridin-5- yl)carbonyl-3-[4-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H

B 261 1-acetyl-5-amino-3-(1,4-benzodioxan-6- yl)amino-1H-1,2,4-triazole

—H —CH₃ D 141 5-amino-3-phenylamino-1-(trans-2-(furan-2-yl)ethenyl)carbonyl-1H-1,2,4- triazole —H —H —H

B 65 5-amino-1-(2,2-dimethyl-2H- benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-3-(4-(iso- propoxy)phenyl)amino-1H-1,2,4-triazole

—H —H

B 68 5-amino-1-(2,2-dimethyl-2H- benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-3-(4-(morpholin-4- yl)phenylamino)-1H-1,2,4-triazole

—H —H

B 78 5-amino-1-(2,2-dimethyl-2H- benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-3-[4-[2-(piperidin-1- yl)ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H

A 86 5-amino-3-[4-[2- (dimethylamino)ethoxy)phenylamino]-1-(2,2-dimethyl-2H-benzo[b[1,4]oxazin-3(4H)-on-6-yl)carbonyl-1H-1,2,4-triazole

—H —H

A 90 5-amino-3-[4-[2- (dimethylamino)propoxy)phenylamino]-1-(2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-1H-1,2,4-triazole

—H —H

B 196 5-amino-1-[2-(bicyclo[2.2.1]hept-5-ene)carbonyl]-3-[4-[2-(pyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H

D 27 5-amino-1-(4- (methoxy)cyclohexyl)carbonyl-3-[4-[2-(piperidin-1-yl)ethoxy)phenylamino]-1H- 1,2,4-triazole

—H —H

B 200 5-amino-1-[2- (bicyclo[2.2.1]heptane)carbonyl]-3-[4-[2-(pyrrolidin-1-yl)ethoxy)phenylamino]-1H- 1,2,4-triazole

—H —H

D 3 5-amino-1-(1H-indol-5-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H

A 5 5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H

A 6 5-amino-1-(1H-indol-2-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H

A 25 5-amino-1-(benzimidazol-6-yl)carbonyl- 3-[4-[2-(pyrroldiin-1-yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H

B 28 5-amino-1-(6-(methyl)pyridin-3- yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H

B 203 5-amino-1-(pyridin-2-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole

—H —H

D 204 5-amino-1-(pyridin-4-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole

—H —H

D 265 5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-(morpholin-4-yl)ethoxy)phenylamino]- 1H-1,2,4-triaozle

—H —H

A 271 5-amino-1-(benzo[d]thiazol-6- yl)carbonyl-3-[4-(2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H

B 279 5-amino-1-(2,3-dihydrobenzofuran-5-yl)carbonyl-3-[4-[2-(pyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H

A 281 5-amino-1-(1H-benzo[d][1,2,3]triazol-5-yl)carbonyl-3-[4-[2-(pyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H

C 283 5-amino-1-(3-methylthien-2-yl)carbonyl- 3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H

A 284 5-amino-1-(5-methylthien-2-yl)carbonyl- 3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H

A 285 5-amino-1-(thien-2-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole

—H —H

A 288 5-amino-1-(quinolin-6-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H

A 295 5-amino-1-(2,2-dimethyl-2H- benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-3-[4-(pyrrolidin-1- yl)phenylamino]-1H-1,2,4-triazole

—H —H

B 309 5-amino-1-(1H-indol-6-yl)carbonyl-3-[3- fluoro-4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—F —H

A 312 5-amino-1-(1,2,3-thiadiazol-4- yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H

D 318 5-amino-1-(1H-indol-6-yl)carbonyl-3-[3-methoxy-4-[2-(pyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—OCH₃ —H

A 323 5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-(azepan-1-yl)ethoxy)phenylamino]- 1H-1,2,4-triazole

—H —H

A 330 5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-(isoindolin-1-yl)ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H

A 365 5-amino-1-(bicyclo[2.2.1]heptan-2-yl)carbonyl-3-[4-(4-methylpiperazin-1- yl)phenylamino]-1H-1,2,4-triazole

—H —H

D 366 5-amino-1-(1H-indol-3-yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H

B 367 5-amino-1-(benzo[b]thiophen-2- yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H

A 369 5-amino-1-(benzo[b]thiophen-5- yl)carbonyl-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H

A 375 5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]- 1H-1,2,4-triazole

—H —H

A 377 5-amino-1-(benzo[b]thiophen-5- yl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H

A 379 5-amino-1-(benzo[b]thiophen-2- yl)carbonyl-3-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H

A 386 5-amino-1-(1,4-benzodioxan-6- yl)carbonyl-3-[4-[2-((S)-3-fluoropyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H

A 388 5-amino-1-(1H-indol-6-yl)carbonyl-3-[4-[2-((S)-3-fluoropyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H

A IC₅₀ activity: A = <1 μM B = 1 to 10 μM C = >10 to 20 μM D = >20 μM

TABLE 4

Cpd # Compound Name R^(1b) R^(1c) R^(1d) R^(3g) IC₅₀ 1403-amino-5-phenylamino-1-(trans-2-(furan-2-yl)ethenyl)carbonyl-1H-1,2,4-triazole —H —H —H

D 66 3-amino-1-(2,2-dimethyl-2H- benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-5-(4-(iso- propoxy)phenyl)amino-1H-1,2,4-triazole

—H —H

B 69 3-amino-1-(2,2-dimethyl-2H- benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-5-(4-(morpholin-4- yl)phenylamino)-1H-1,2,4-triazole

—H —H

B 202 3-amino-1-(1H-indol-5-yl)carobnyl-5-[4-[2-(pyrrolidin-1-yl)ethoxy)phenylamino]-1H- 1,2,4-triazole

—H —H

B 296 3-amino-1-(2,2-dimethyl-2H- benzo[b][1,4]oxazin-3(4H)-on-6-yl)carbonyl-5-[4-(pyrrolidin-1- yl)phenylamino]-1H-1,2,4-triazole

—H —H

C 368 3-amino-1-(benzo[b]thiophen-2- yl)carbonyl-5-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H

B 376 3-amino-1-(1H-indol-6-yl)carbonyl-5-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole

—H —H

A 378 3-amino-1-(benzo[b]thiophen-5- yl)carbonyl-5-[4-[2-(imidazol-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H

A 387 3-amino-1-(1,4-benzodioxan-6-yl)carbonyl-5-[4-[2-((S)-3-fluoropyrrolidin-1-yl)ethoxy]phenylamino]-1H-1,2,4- triazole

—H —H

A 389 3-amino-1-(1H-indol-6-yl)carbonyl-5-[4-[2-((S)-3-fluoropyrrolidin-1- yl)ethoxy]phenylamino]-1H-1,2,4-triazole

—H —H

A IC₅₀ activity: A = <1 μM B = 1 to 10 μM C = >10 to 20 μM D = >20 μM

TABLE 5

Cpd # Compound Name R¹ R^(3b) R^(3c) R^(3d) R^(3e) R^(3f) R² IC₅₀ 1035-amino-3-(2- (ethoxycarbonyl)benzo- furan-5-yl)amino-1-(3-(iso-propoxy)phenyl)carbonyl- 1H-1,2,4-triazole

—H

—H —H —H —H D 130 5-amino-3-[N-(2-(tetra- hydropy-ran-2-yloxy)methylbenzo-furan-5-yl) amino]-1-(3- (methyl)phenyl)carbonyl-1H-1,2,4-triazole

—H —CH₃ —H —H —H —H B 136 5-amino-3-(2- (hydroxymethyl)benzo-furan-5-yl)amino-1-(3- (methyl)phenyl)carbonyl- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H B 154 5-amino-3-(indazol-5-yl)amino-1-(3-(methyl)phenyl) carbonyl-1H-1,2,4-triazole

—H —CH₃ —H —H —H —H B 160 5-amino-3-(indazol-6-yl)amino-1-(3-(methyl)phenyl) carbonyl-1H-1,2,4-triazole

—H —CH₃ —H —H —H —H B 161 5-amino-3-(benzo[b][1,4] oxazin-3(4H)-on-6-yl)amino-1-(3-(methylphenyl) carbonyl-1H-1,2,4-triazole

—H —CH₃ —H —H —H —H D 206 5-amino-3-[(2H,3H-4-tert-butoxycarbonylbenzo[1,4] oxazin-6-yl)amino]-1-(3-methylphenyl)carbonyl-1, 2,4-triazole

—H —CH₃ —H —H —H —H D 207 5-amino-1-(3- methylphenyl)carbonyl-3-[2-[N-[2-(tetrahydropyran- 2-yloxy)ethyl]amino] carbonyl-benzofuran-5-yl]amino-1H-1,2,4-triazole

—H —CH₃ —H —H —H —H B 208 5-amino-3-[2-[2- hydroxyethyl- aminocarbonyl]-benzofuran-5-yl]amino- 1-(3-methylphenyl) carbonyl-1H-1,2,4-triazole

—H —CH₃ —H —H —H —H B 215 5-amino-3-[(3,4- dihydrobenzo[1,4]oxazin-6-yl)amino]-1-(3- methylphenyl)carbonyl- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H D 219 5-amino-3-[2- (ethoxycarbonyl)benzo-furan-5-yl]amino-1-(3- methylphenyl)carbonyl- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H B 220 5-amino-1-(3- methylphenyl)carbonyl-3-(pyridin-3-yl)amino- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H D 222 5-amino-3-(2-methyl-2H-indazol-5yl)amino-1-(3- methylphenyl)carbonyl- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H D (Ia- 28) 5-amino-3-(2-((allyl(methyl)amino)methyl)- benzofuran-5-yl)amino- 1-(3-methyl-phenyl)carbonyl- 1H-1,2,4-triazole

—H —CH —H —H —H —H B 227 5-amino-3-[1-methyl-1H-indazol-5-yl]amino-1-(3- methylphenyl)carbonyl- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H B (Ia- 29) 5-amino-3-(2- ((methylamino)methyl)benzo-furan-5-yl)amino-1- (3-methylphenyl)carbonyl- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H A 229 5-amino-3-(benzofuran-5- yl)amino-1-(3-methyl-phenyl)carbonyl- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H B 250 5-amino-3-(benzothiazol-6-yl)amino-1-(3-methyl- phenyl)carbonyl- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H B 251 5-amino-1-(3- methylphenyl)carbonyl-3-(6-quinolinyl)aminio- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H B 252 5-amino-3-(1H-indol-5- yl)amino-1-(3-methyl-phenyl)-carbonyl- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H B 253 5-amino-3-(1H-2-methyl-indazol-6-yl)amino-1-(3- methylphenyl)carbonyl- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H B 254 5-amino-3-(1H-1-methyl-indazol-6-yl)amino-1-(3- methylphenyl)carbonyl- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H D 255 5-amino-3-(1H-2-methyl- indol-5-yl)amino-1-(3-methylphenyl)carbonyl- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H B 256 5-amino-3-(benzothiazol-2-yl)amino-1-(3-methyl- phenyl)carbonyl- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H D 259 5-amino-3-(1,2-benziso-thiazol-5-yl)amino-1-(3- methylphenyl)carbonyl- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H D 260 5-amino-3-(3-methyl-1,2-benzisothiazol-5-yl)amino- 1-(3-methylphenyl) carbonyl-1H-1,2,4-triazole

—H —CH₃ —H —H —H —H D  63 5-amino-3-(2,2-difluoro-2H-benzo[b][1,4]oxazin- 3(4H)-on-6-yl)amino-1- (4-(iso-propoxy)phenyl)carbonyl-1H-1,2,4-triazole

—H —H —H —H —H D  64 5-amino-3-(2,2-difluoro- 2H-benzo[b][1,4]oxazin-3(4H)-on-6-yl)amino-1- (3-(methyl)phenyl)carbonyl- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H D 273 5-amino-1-(4-(tert-butyl)phenyl)carbonyl-3-[4- ((tert-butoxycarbonyl)amino-chroman-6-yl]amino- 1H-1,2,4-triazole

—C(CH₃)₃ —H —H —H —H —H D 274 5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3- [4-((tert-butoxycarbonyl)amino-chroman-6-yl]amino- 1H-1,2,4-triazole

—H —H —H —H —H D 275 5-amino-1-(4-(tert- butoxy)phenyl)carbonyl-3-[4-((tert-butoxycarbonyl) amino-chroman-6-yl]amino- 1H-1,2,4-triazole

—OC(CH₃)₃ —H —H —H —H —H D 346 5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3- [(5-(aminocarbonyl)bicyclo[2.2.1]-hept-2-en-6-yl) amino]-1H-1,2,4-triazole

—OC(CH₃)₃ —H —H —H —H —H D 348 5-amino-1-(3-(tert-butoxy)phenyl)carbonyl-3- [(5-(aminocarbonyl)bicyclo[2.2.1]-hept-2-en-6-yl) amino]-1H-1,2,4-triazole

—H —OC(CH₃)₃ —H —H —H —H D 350 5-amino-1-(4-(dimethyl-amino)phenyl)carbonyl- 3-[(5-(aminocarbonyl)- bicyclo[2.2.1]hept-2-en-6-yl)amino]-1H-1,2,4-triazole

—N(CH₃)₃ —H —H —H —H —H D 352 5-amino-1-(3-(dimethyl-amino)phenyl)carbonyl- 3-[(5-(aminocarbonyl)- bicyclo[2.2.1]hept-2-en-6-yl)amino]-1H-1,2,4-triazole

—H —N(CH₃)₃ —H —H —H —H D 354 5-amino-1-(4-(iso-propoxy)phenyl)carbonyl-3-[(5- (aminocarbonyl)bicyclo [2.2.1]-hept-2-en-6-yl)amino]-1H-1,2,4-triazole

—H —H —H —H —H D 392 5-amino-1-(2,6- difluorophenyl)carbonyl-3-(1-methylsulfonylpiperidin- 4-yl)amino-1H-1, 2,4-triazole

—H —H —F —H —F —H D 393 5-amino-1-(4-(tert- butoxy)phenyl)carbonyl-3-(1-methylsulfonylpiperidin- 4-yl)amino-1H-1, 2,4-triazole

—OC(CH₃)₃ —H —H —H —H —H D 394 5-amino-1-(4-(tert-butoxy)phenyl)carbonyl-3- (1-methylsulfonylpiperidin- 4-yl)amino-1H-1,2,4-triazole

—H —H —H —H —H D 395 5-amino-1-(4- (dimethylamino)phenyl) carbonyl-3-(1-methylsulfonyl-piperidin-4- yl)amino-1H-1,2,4-triazole

—N(CH₃)₂ —H —H —H —H —H -D 399 5-amino-1-(4-(morpholin-4-yl)phenyl)carbonyl-3-(1- methylsulfonylpiperidin-4-yl)amino-1H-1,2,4-triazole

—H —H —H —H —H D 403 5-amino-3-[N-(3-(4-(2- chloro-6-fluorophenyl)piperazin-1-yl)prop-1- yl)-N-((3-methylphenyl) carbonyl)amino]-1-(3-methylphenyl) carbonyl-1H-1,2,4-triazole

—H —CH₃ —H —H —H

D 405 5-amino-3-[3-(4-(2-chloro- 6-fluorophenyl)piperazin-1-yl)prop-1-yl]amino-1-(3- methylphenyl)carbonyl- 1H-1,2,4-triazole

—H —CH₃ —H —H —H —H D IC₅₀ activity: A = <1 μM B = 1 to 10 μM C = >10 to20 μM D = >20 μM

TABLE 6

Cpd # Compound Name R^(1e) R^(3b) R^(3c) R^(3d) R^(3e) R^(3f) IC₅₀ 1673-amino-5-[(2H,3H-4-tert- butoxycarbonylbenzo[1,4]oxazin-6-yl)amino]-1-(3-(methyl)phenyl)carbonyl- 1H-1,2,4-triazole

—H —CH₃ —H —H D 345 3-amino-1-(4-(tert-butoxy)phenyl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2-yl)amino]-1H-1,2,4-triazole

—OC(CH₃)₃ —H —H —H D 347 3-amino-1-(3-(tert-butoxy)phenyl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2-yl)amino]-1H-1,2,4-triazole

—H —OC(CH₃)₃ —H —H D 349 3-amino-1-(4-(dimethylamino)phenyl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2- yl)amino]-1H-1,2,4-triazole

—N(CH₃)₂ —H —H —H D 351 3-amino-1-(3-(dimethylamino)phenyl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2- yl)amino]-1H-1,2,4-triazole

—H —N(CH₃)₂ —H —H D 353 3-amino-1-(4-(iso-propoxy)phenyl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2-yl)amino]-1H-1,2,4- triazole

—H —H —H D 391 3-amino-1-(2,6-difluorophenyl)carbonyl-5-(1-methylsulfonylpiperidin-4-yl)amino- 1H-1,2,4-triazole

—H —H —F —H —F D 396 3-amino-1-(4- (dimethylamino)phenyl)carbonyl-5-(1-methylsulfonylpiperidin-4-yl)amino-1H- 1,2,4-triazole

—N(CH₃)₂ —H —H —H —H D 404 3-amino-5-[3-(4-(2-chloro-6-fluorophenyl)piperazin-1-yl)prop-1-yl]amino-1-(3-methylphenyl)carbonyl-1H- 1,2,4-triazole

—H —CH₃ —H —H —H D IC₅₀ activity: A = <1 μM B = 1 to 10 μM C = >10 to 20μM D = >20 μM

TABLE 7

Cpd # Compound Name R^(1b) R^(1c) R^(1d) Y Z R^(3g) IC₅₀ 1725-amino-N-(4-chlorophenyl)-3-[4-(methoxy)phenylamino]-1H-1,2,4-triazole- 1-carboxamide —OCH₃ —H —H O—N(H)—

D 174 3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-(4-chlorophenyl)-1H-1,2,4- triazole-1-carboxamide

—H —H O —N(H)—

D 175 3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-(1,3-benzodioxol-5-yl)-1H- 1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

B 177 3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-cyclopentyl-1H-1,2,4-triazole- 1-carboxamide

—H —H O —N(H)—

D 179 3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-(4-(iso-propyl)phenyl)-1H- 1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

B 180 3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-(4-(butoxy)phenyl)-1H-1,2,4- triazole-1-carboxamide

—H —H O —N(H)—

B 41 5-amino-N-(4-(iso-propyl)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

B 46 5-amino-N-(4-butoxyphenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

B 39 5-amino-N-(4-methylphenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

B 40 5-amino-N-(4-(methoxy)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

B 185 3-[4-(acetyl(methyl)amino)phenyl]amino-5-amino-N-cyclohexyl-1H-1,2,4-triazole-1- carboxamide

—H —H O —N(H)—

D 35 5-amino-N-(1,3-benzodioxol-5-yl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

B 29 5-amino-N-(3-methylphenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

A 30 5-amino-N-(3-methoxyphenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

A 33 5-amino-N-(3,5-(dimethoxy)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]- 1H-1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

A 42 5-amino-N-cyclohexyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole- 1-carboxamide

—H —H O —N(H)—

B 45 5-amino-N-cyclopentyl-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4- triazole-1-carboxamide

—H —H O —N(H)—

B 37 5-amino-N-(4-methylphenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

B 32 5-amino-N-(3-methoxyphenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

A 194 5-amino-N-(4-cyanophenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

D 36 5-amino-N-(1,3-benzodioxol-5-yl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

B 31 5-amino-N-(3-methylphenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

A 34 5-amino-N-(3,5-(dimethoxy)phenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]- 1H-1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

A 43 5-amino-N-(3,4-(dimethoxy)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]- 1H-1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

B 38 5-amino-N-(3,4-(dimethyl)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

B 199 5-amino-N-(3,5-(dimethyl)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

D 44 5-amino-N-(4-(dimethylamino)phenyl)-3-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole-1-carboxamide

—H —H O —N(H)—

B 201 5-amino-3-[4-(piperidin-1-yl)phenylamino]-1-(tert-butoxycarbonyl)- 1H-1,2,4-triazole

—H —H O O

D 325 5-amino-N-(2,4,6-trifluorophenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carbothioamide

—H —H S —N(H)—

B 326 5-amino-N-(2,6-difluorophenyl)-3-[4-[2-(pyrrolidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carbothioamide

—H —H S —N(H)—

A IC₅₀ activity: A = <1 μM B = 1 to 10 μM C = >10 to 20 μM D = >20 μM

TABLE 8

Cpd # Compound Name R^(1b) R^(1c) R^(1d) Z R^(3g) IC₅₀ 933-amino-5-(1,4-benzodioxan-6-yl)amino-1-methoxycarbonyl-1H-1,2,4-triazole

—H O —CH₃ D 173 5-amino-3-(4-methoxyphenyl)amino-1-(tert-butoxycarbonyl)-1H-1,2,4-triazole —OCH₃ —H —H O —C(CH₃)₃ 1765-[4-(acetyl(methyl)amino)phenyl]amino-3-amino-N-(1,3-benzodioxol-5-yl)-1H- 1,2,4-triazole-1-carboxamide

—H —H —N(H)—

D 178 5-[4-(acetyl(methyl)amino)phenyl]amino-3-amino-N-cyclopentyl-1H-1,2,4-triazole- 1-carboxamide

—H —H —N(H)—

D 182 3-amino-N-(4-(butoxy)phenyl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H —N(H)—

D 183 3-amino-N-(4-(methyl)phenyl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H —N(H)—

B 184 3-amino-N-(4-(methoxy)phenyl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H —N(H)—

B 186 3-[4-(acetyl(methyl)amino)phenyl]amino-3-amino-N-cyclohexyl-1H-1,2,4-triazole-1- carboxamide

—H —H —N(H)—

D 187 3-amino-N-(3-(methyl)phenyl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H —N(H)—

B 188 3-amino-N-(3,5-dimethoxyphenyl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H —N(H)—

B 189 3-amino-N-cyclohexyl-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4-triazole- 1-carboxamide

—H —H —N(H)—

B 190 3-amino-N-cyclopentyl-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H-1,2,4- triazole-1-carboxamide

—H —H —N(H)—

D 193 3-amino-N-(1,3-benzodioxol-5-yl)-5-[4-[2-(piperidin-1-yl)ethoxy]phenylamino]-1H- 1,2,4-triazole-1-carboxamide

—H —H —N(H)—

B IC₅₀ activity: A = <1 μM B = 1 to 10 μM C = >10 to 20 μM D = >20 μM

TABLE 9

Cpd # Compound Name R^(1e) R^(3g) IC₅₀ 2765-amino-1-(1H-indol-6-yl)carbonyl-3-[4-((tert-butoxycarbonyl)aminochroman-6- yl]amino-1H-1,2,4-triazole

B 356 5-amino-1-(1H-indol-6-yl)carbonyl-3-[(5-(aminocarbonyl)bicyclo[2.2.1]hept-2-en-6- yl)amino]-1H-1,2,4-triazole

D 397 5-amino-1-(1,4-benzodioxan-6-yl)carbonyl-3-(1-methylsulfonylpiperidin-4- yl)amino-1H-1,2,4-triazole

D 398 5-amino-1-(1H-indol-6-yl)carbonyl-3-(1-methylsulfonylpiperidin-4-yl)amino-1H- 1,2,4-triazole

IC₅₀ activity: A = <1 μM B = 1 to 10 μM C = >10 to 20 μM D = >20 μM

TABLE 10

Cpd # Compound Name R^(1e) R^(3g) IC₅₀ 3553-amino-1-(1H-indol-6-yl)carbonyl-5-[(3-(aminocarbonyl)bicyclo[2.2.1]hept-5-en-2- yl)amino]-1H-1,2,4-triazole

D IC₅₀ activity: A = <1 μM B = 1 to 10 μM C = >10 to 20 μM D = >20 μM

All of the U.S. patents, U.S. patent application publications, U.S.patent applications, foreign patents, foreign patent applications andnon-patent publications referred to in this specification and/or listedin the Application Data Sheet are incorporated herein by reference, intheir entireties.

From the foregoing it will be appreciated that, although specificembodiments of the invention have been described herein for purposes ofillustration, various modifications may be made without deviating fromthe spirit and scope of the invention. Accordingly, the invention is notlimited except as by the appended claims.

1. A method of treating a disease or condition associated with Axlcatalytic activity in a mammal, wherein the method comprisesadministering to the mammal a therapeutically effective amount of acompound of formula (Ia) or formula (Ib):

wherein, independently at each occurrence: A is —C(O)— or —C(S)—; R¹ isaryl substituted with at least one of —R⁸—OR¹⁰ or —R⁸—O—R⁹—CN, whereeach R⁸ is a direct bond and R¹⁰ is selected from the group consistingof optionally substituted heterocyclylalkyl, optionally substitutedheteroarylalkyl and optionally substituted aralkyl, and optionallysubstituted with one or more substituents selected from the groupconsisting of halo, haloalkyl, alkyl, optionally substituted heteroaryl,optionally substituted heterocyclyl, and alkoxy; R², R⁴ and R⁵ are eachindependently hydrogen, alkyl, aryl, aralkyl, —C(O)R¹⁰ or —C(O)N(R⁶)R⁷;R³ is one of the following: a) aryl optionally substituted with one ormore substituents selected from the group consisting of alkyl, halo;haloalkyl, nitro, cycloalkyl, cycloalkylalkyl, optionally substitutedaryl, optionally substituted heteroaryl, optionally substitutedheterocyclyl, —R⁸—OR¹⁰, —R⁸—C(O)OR¹⁰, —R⁸—OC(O)R¹⁰, —R⁸—O—R⁹—C(O)OR¹⁰,—R⁸—O—R⁹—C(O)N(R⁶)R⁷, —S(O)_(p)R⁶ (where p is 0, 1 or 2),—S(O)_(t)N(R⁶)R⁷ (where t is 1 or 2), —R⁸—N(R⁶)R⁷, —R⁸—N(R⁶)C(O)R¹⁰,—R⁸—N(R⁶)C(O)OR¹⁰ and —R⁸—CN; or b) optionally substituted heteroaryl;R⁶ and R⁷ are each independently selected from the group consisting ofhydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl,hydroxyalkyl, optionally substituted aryl, optionally substitutedaralkyl, optionally substituted aralkenyl, optionally substitutedaralkynyl, optionally substituted cycloalkyl, optionally substitutedcycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionallysubstituted cycloalkylalkynyl, optionally substituted heterocyclyl,optionally substituted heterocyclylalkyl, optionally substitutedheterocyclylalkenyl, optionally substituted heterocyclylalkynyl,optionally substituted heteroaryl, optionally substitutedheteroarylalkyl, optionally substituted heteroarylalkenyl, optionallysubstituted heteroarylalkynyl, —R⁹—CN, —R⁹—NO₂, —R⁹—N(R¹⁰)₂,—R⁹—C(O)OR¹⁰ and —R⁹—C(O)N(R¹⁰)₂; optionally, R⁶ and R⁷, together withthe nitrogen to which they are attached, form an optionally substitutedN-heteroaryl or an optionally substituted N-heterocyclyl; each R⁸present in a R³ substituent is independently selected from the groupconsisting of a direct bond, an optionally substituted straight orbranched alkylene chain, an optionally substituted straight or branchedalkenylene chain and an optionally substituted straight or branchedalkynylene chain; each R⁹ is independently selected from the groupconsisting of an optionally substituted straight or branched alkylenechain, an optionally substituted straight or branched alkenylene chainand an optionally substituted straight or branched alkynylene chain; andR¹⁰ present in the R², R⁴ and R⁵ substituents and each R¹⁰ present in aR³ substituent, a R⁶ substituent or a R⁷ substituent is independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,haloalkyl, haloalkenyl, haloalkynyl, optionally substituted aryl,optionally substituted aralkyl, optionally substituted aralkenyl,optionally substituted aralkynyl, optionally substituted cycloalkyl,optionally substituted cycloalkylalkyl, optionally substitutedcycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionallysubstituted heterocyclyl, optionally substituted heterocyclylalkyl,optionally substituted heterocyclylalkenyl, optionally substitutedheterocyclylalkynyl, optionally substituted heteroaryl, optionallysubstituted heteroarylalkyl, optionally substituted heteroarylalkenyl,and optionally substituted heteroarylalkynyl; as an isolatedstereoisomer or tautomer thereof or mixtures thereof, or apharmaceutically acceptable salt or N-oxide thereof.
 2. The method ofclaim 1 wherein the disease or condition associated with Axl catalyticactivity is selected from the group consisting of endometriosis,rheumatoid arthritis, psoriasis, visual impairment due to maculardegeneration, diabetic retinopathy, retinopathy of prematurity,osteoarthritis, cataracts, vascular diseases selected from the groupconsisting of restenosis, atherosclerosis, and thrombosis, vascularinjury, kidney diseases selected from the group consisting ofglomerulonephritis, diabetic nephropathy and renal transplant rejection,solid tumors selected from the group consisting of breast carcinoma,renal carcinoma, endometrial carcinoma, ovarian carcinoma, thyroidcarcinoma, non-small cell lung carcinoma, prostate carcinoma, gastriccancer and uveal melanoma, and liquid tumors selected from the groupconsisting of myeloid leukemia and lymphoma.
 3. The method of claim 2wherein the disease or condition is selected from the group consistingof rheumatoid arthritis, vascular disease selected from the groupconsisting of restenosis, atherosclerosis and thrombosis, and vascularinjury, psoriasis, visual impairment due to macular degeneration,diabetic retinopathy, retinopathy of prematurity, kidney diseaseselected from the group consisting of glomerulonephritis, diabeticnephropathy and renal transplant rejection, osteoarthritis, andcataracts.
 4. The method of claim 2, wherein the disease or condition issolid tumors selected from the group consisting of breast carcinoma,renal carcinoma, endometrial carcinoma, ovarian carcinoma, thyroidcarcinoma, non-small cell lung carcinoma, prostate carcinoma, gastriccancer and uveal melanoma.
 5. The method of claim 2, wherein the diseaseor condition is liquid tumors selected from the group consisting ofleukemia and lymphoma.
 6. The method of claim 2 wherein the disease orcondition is endometriosis.